RBCC

Full text data of G6PD

G6PD [Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Glucose-6-phosphate 1-dehydrogenase; G6PD; 1.1.1.49
Note: presumably soluble (membrane word is not in UniProt keywords or features)

hRBCD IPI00216008
IPI00216008 Splice Isoform 2 Of Glucose-6-phosphate 1-dehydrogenase short Produces pentose sugars for nucleic acid synthesis and main producer of NADPH reducing power soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic isoform 1 or 2 found at its expected molecular weight found at molecular weight

UniProt P11413
ID G6PD_HUMAN Reviewed; 515 AA.
AC P11413; D3DWX9; Q16000; Q16765; Q8IU70; Q8IU88; Q8IUA6; Q96PQ2;
read moreDT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 4.
DT 22-JAN-2014, entry version 190.
DE RecName: Full=Glucose-6-phosphate 1-dehydrogenase;
DE Short=G6PD;
DE EC=1.1.1.49;
GN Name=G6PD;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT).
RX PubMed=3515319; DOI=10.1093/nar/14.6.2511;
RA Persico M.G., Viglietto G., Martini G., Toniolo D., Paonessa G.,
RA Moscatelli C., Dono R., Vulliamy T.J., Luzzatto L., D'Urso M.;
RT "Isolation of human glucose-6-phosphate dehydrogenase (G6PD) cDNA
RT clones: primary structure of the protein and unusual 5' non-coding
RT region.";
RL Nucleic Acids Res. 14:2511-2522(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2428611;
RA Martini G., Toniolo D., Vulliamy T., Luzzatto L., Dono R.,
RA Viglietto G., Paonessa G., D'Urso M., Persico M.G.;
RT "Structural analysis of the X-linked gene encoding human glucose 6-
RT phosphate dehydrogenase.";
RL EMBO J. 5:1849-1855(1986).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT), PARTIAL NUCLEOTIDE
RP SEQUENCE [MRNA] (ISOFORM LONG), AND VARIANTS MET-68 AND ASP-126.
RX PubMed=2836867; DOI=10.1073/pnas.85.11.3951;
RA Hirono A., Beutler E.;
RT "Molecular cloning and nucleotide sequence of cDNA for human glucose-
RT 6-phosphate dehydrogenase variant A(-).";
RL Proc. Natl. Acad. Sci. U.S.A. 85:3951-3954(1988).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS MET-68 AND ASP-126.
RX PubMed=1889820; DOI=10.1016/0888-7543(91)90465-Q;
RA Chen E.Y., Cheng A., Lee A., Kuang W., Hillier L., Green P.,
RA Schlessinger D., Ciccodicola A., D'Urso M.;
RT "Sequence of human glucose-6-phosphate dehydrogenase cloned in
RT plasmids and a yeast artificial chromosome.";
RL Genomics 10:792-800(1991).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS MET-68 AND ASP-126.
RX PubMed=8733135; DOI=10.1093/hmg/5.5.659;
RA Chen E.Y., Zollo M., Mazzarella R.A., Ciccodicola A., Chen C.-N.,
RA Zuo L., Heiner C., Burough F.W., Ripetto M., Schlessinger D.,
RA D'Urso M.;
RT "Long-range sequence analysis in Xq28: thirteen known and six
RT candidate genes in 219.4 kb of high GC DNA between the RCP/GCP and
RT G6PD loci.";
RL Hum. Mol. Genet. 5:659-668(1996).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A.,
RA Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G.,
RA Jones M.C., Hurles M.E., Andrews T.D., Scott C.E., Searle S.,
RA Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R.,
RA Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L.,
RA Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A.,
RA Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S.,
RA Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R.,
RA Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M.,
RA Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N.,
RA Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D.,
RA Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W.,
RA Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C.,
RA Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C.,
RA Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J.,
RA Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S.,
RA Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I.,
RA Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L.,
RA Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P.,
RA Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S.,
RA Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A.,
RA Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J.,
RA Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J.,
RA Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S.,
RA de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z.,
RA Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C.,
RA Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W.,
RA Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T.,
RA Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I.,
RA Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N.,
RA Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J.,
RA Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E.,
RA Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S.,
RA Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T.,
RA Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S.,
RA Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L.,
RA Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A.,
RA Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L.,
RA Williams G., Williams L., Williamson A., Williamson H., Wilming L.,
RA Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H.,
RA Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A.,
RA Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A.,
RA Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T.,
RA Gibbs R.A., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM SHORT).
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-71.
RX PubMed=2758468; DOI=10.1016/0092-8674(89)90440-6;
RA Kanno H., Huang I.Y., Kan Y.W., Yoshida A.;
RT "Two structural genes on different chromosomes are required for
RT encoding the major subunit of human red cell glucose-6-phosphate
RT dehydrogenase.";
RL Cell 58:595-606(1989).
RN [10]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-71 (ISOFORM 3).
RX PubMed=8466644; DOI=10.1089/dna.1993.12.209;
RA Kanno H., Kondoh T., Yoshida A.;
RT "5' structure and expression of human glucose-6-phosphate
RT dehydrogenase mRNA.";
RL DNA Cell Biol. 12:209-215(1993).
RN [11]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-15.
RX PubMed=1874446; DOI=10.1016/0378-1119(91)90078-P;
RA Toniolo D., Filippi M., Dono R., Lettieri T., Martini G.;
RT "The CpG island in the 5' region of the G6PD gene of man and mouse.";
RL Gene 102:197-203(1991).
RN [12]
RP PROTEIN SEQUENCE OF 2-9.
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A.,
RA Thomas G.R., Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass
RT spectrometric identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [13]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 30-34, AND VARIANT CSNA ARG-32.
RX PubMed=1945893; DOI=10.1093/nar/19.21.6056;
RA Chao L.T., Du C.S., Louie E., Zuo L., Chen E., Lubin B., Chiu D.T.;
RT "A to G substitution identified in exon 2 of the G6PD gene among G6PD
RT deficient Chinese.";
RL Nucleic Acids Res. 19:6056-6056(1991).
RN [14]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 41-515 (ISOFORM SHORT), AND
RP VARIANTS MET-68 AND ASP-126.
RX PubMed=12524354;
RA Saunders M.A., Hammer M.F., Nachman M.W.;
RT "Nucleotide variability at G6pd and the signature of malarial
RT selection in humans.";
RL Genetics 162:1849-1861(2002).
RN [15]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 154-515 (ISOFORM SHORT).
RX PubMed=3012556; DOI=10.1073/pnas.83.12.4157;
RA Takizawa T., Huang I.-Y., Ikuta T., Yoshida A.;
RT "Human glucose-6-phosphate dehydrogenase: primary structure and cDNA
RT cloning.";
RL Proc. Natl. Acad. Sci. U.S.A. 83:4157-4161(1986).
RN [16]
RP PROTEIN SEQUENCE OF 199-215.
RX PubMed=3126064; DOI=10.1111/j.1432-1033.1988.tb13815.x;
RA Camardella L., Caruso C., Rutigliano B., Romano M., di Prisco G.,
RA Descalzi-Cancedda F.;
RT "Human erythrocyte glucose-6-phosphate dehydrogenase. Identification
RT of a reactive lysyl residue labelled with pyridoxal 5'-phosphate.";
RL Eur. J. Biochem. 171:485-489(1988).
RN [17]
RP PROTEIN SEQUENCE OF 509-515.
RX PubMed=6696761; DOI=10.1016/0006-291X(84)91105-7;
RA Descalzi-Cancedda F., Caruso C., Romano M., di Prisco G.,
RA Camardella L.;
RT "Amino acid sequence of the carboxy-terminal end of human erythrocyte
RT glucose-6-phosphate dehydrogenase.";
RL Biochem. Biophys. Res. Commun. 118:332-338(1984).
RN [18]
RP ALTERNATIVE SPLICING.
RX PubMed=2910917; DOI=10.1172/JCI113881;
RA Hirono A., Beutler E.;
RT "Alternative splicing of human glucose-6-phosphate dehydrogenase
RT messenger RNA in different tissues.";
RL J. Clin. Invest. 83:343-346(1989).
RN [19]
RP ACETYLATION AT ALA-2, AND MASS SPECTROMETRY.
RX PubMed=7857286; DOI=10.1006/bbrc.1995.1192;
RA Camardella L., Damonte G., Carratore V., Benatti U., Tonetti M.,
RA Moneti G.;
RT "Glucose 6-phosphate dehydrogenase from human erythrocytes:
RT identification of N-acetyl-alanine at the N-terminus of the mature
RT protein.";
RL Biochem. Biophys. Res. Commun. 207:331-338(1995).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-26 (ISOFORM 3), AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [21]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [22]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-89; LYS-171; LYS-403;
RP LYS-432 AND LYS-497, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [23]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [24]
RP REVIEW.
RX PubMed=22431005; DOI=10.1002/iub.1017;
RA Stanton R.C.;
RT "Glucose-6-phosphate dehydrogenase, NADPH, and cell survival.";
RL IUBMB Life 64:362-369(2012).
RN [25]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [26]
RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF VARIANT CANTON IN COMPLEX
RP WITH NADP, AND SUBUNIT.
RX PubMed=10745013; DOI=10.1016/S0969-2126(00)00104-0;
RA Au S.W., Gover S., Lam V.M., Adams M.J.;
RT "Human glucose-6-phosphate dehydrogenase: the crystal structure
RT reveals a structural NADP(+) molecule and provides insights into
RT enzyme deficiency.";
RL Structure 8:293-303(2000).
RN [27]
RP REVIEW ON VARIANTS.
RX PubMed=8364584; DOI=10.1002/humu.1380020302;
RA Vulliamy T., Beutler E., Luzzatto L.;
RT "Variants of glucose-6-phosphate dehydrogenase are due to missense
RT mutations spread throughout the coding region of the gene.";
RL Hum. Mutat. 2:159-167(1993).
RN [28]
RP REVIEW ON VARIANTS.
RX PubMed=11857737; DOI=10.1002/humu.10036;
RA Kwok C.J., Martin A.C., Au S.W., Lam V.M.;
RT "G6PDdb, an integrated database of glucose-6-phosphate dehydrogenase
RT (G6PD) mutations.";
RL Hum. Mutat. 19:217-224(2002).
RN [29]
RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 28-514 IN COMPLEX WITH NADP
RP AND GLUCOSE 6-PHOSPHATE, FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND SUBUNIT.
RX PubMed=15858258; DOI=10.1107/S0907444905002350;
RA Kotaka M., Gover S., Vandeputte-Rutten L., Au S.W., Lam V.M.,
RA Adams M.J.;
RT "Structural studies of glucose-6-phosphate and NADP+ binding to human
RT glucose-6-phosphate dehydrogenase.";
RL Acta Crystallogr. D 61:495-504(2005).
RN [30]
RP VARIANT A(+) ASP-126.
RX PubMed=3446582; DOI=10.1016/0888-7543(87)90048-6;
RA Takizawa T., Yoneyama Y., Miwa S., Yoshida A.;
RT "A single nucleotide base transition is the basis of the common human
RT glucose-6-phosphate dehydrogenase variant A (+).";
RL Genomics 1:228-231(1987).
RN [31]
RP VARIANTS.
RX PubMed=3393536; DOI=10.1073/pnas.85.14.5171;
RA Vulliamy T.J., D'Urso M., Battistuzzi G., Estrada M., Foulkes N.S.,
RA Martini G., Calabro V., Poggi V., Giordano R., Town M., Luzzatto L.,
RA Persico M.G.;
RT "Diverse point mutations in the human glucose-6-phosphate
RT dehydrogenase gene cause enzyme deficiency and mild or severe
RT hemolytic anemia.";
RL Proc. Natl. Acad. Sci. U.S.A. 85:5171-5175(1988).
RN [32]
RP VARIANTS SASSARI/CAGLIARI PHE-188 AND SEATTLE HIS-282.
RX PubMed=2912069;
RA de Vita G., Alcalay M., Sampietro M., Cappelini M.D., Fiorelli G.,
RA Toniolo D.;
RT "Two point mutations are responsible for G6PD polymorphism in
RT Sardinia.";
RL Am. J. Hum. Genet. 44:233-240(1989).
RN [33]
RP VARIANTS GLN-227 AND SER-353, AND VARIANTS NSHA CYS-387; LEU-394;
RP ASP-410 AND PRO-439.
RX PubMed=1611091;
RA Beutler E., Westwood B., Prchal J.T., Vaca C.S., Bartsocas C.S.,
RA Baronciani L.;
RT "New glucose-6-phosphate dehydrogenase mutations from various ethnic
RT groups.";
RL Blood 80:255-256(1992).
RN [34]
RP VARIANT NASHVILLE/ANAHEIM HIS-393.
RX PubMed=1536798; DOI=10.1111/j.1365-2141.1992.tb06409.x;
RA Filosa S., Calabro V., Vallone D., Poggi V., Mason P., Pagnini D.,
RA Alfinito F., Rotoli B., Martini G., Luzzatto L., Battistuzzi G.;
RT "Molecular basis of chronic non-spherocytic haemolytic anaemia: a new
RT G6PD variant (393arg-to-his) with abnormal K(m) G6P and marked in vivo
RT instability.";
RL Br. J. Haematol. 80:111-116(1992).
RN [35]
RP VARIANT CHINESE-2/MAEWO CYS-454.
RX PubMed=1303180; DOI=10.1093/hmg/1.3.205;
RA Perng L.-I., Chiou S.-S., Liu T.-C., Chang J.-G.;
RT "A novel C to T substitution at nucleotide 1360 of cDNA which
RT abolishes a natural Hha I site accounts for a new G6PD deficiency gene
RT in Chinese.";
RL Hum. Mol. Genet. 1:205-205(1992).
RN [36]
RP VARIANT KALYAN/KERALA LYS-317.
RX PubMed=1303182; DOI=10.1093/hmg/1.3.209;
RA Ahluwalia A., Corcoran C.M., Vulliamy T.J., Ishwad C.S., Naidu J.M.,
RA Stevens D.J., Mason P.J., Luzzatto L.;
RT "G6PD Kalyan and G6PD Kerala; two deficient variants in India caused
RT by the same 317 Glu-->Lys mutation.";
RL Hum. Mol. Genet. 1:209-210(1992).
RN [37]
RP VARIANT AURES THR-48.
RX PubMed=8490627; DOI=10.1093/hmg/2.1.81;
RA Nafa K., Reghis A., Osmani N., Baghli L., Benabadji M., Kaplan J.-C.,
RA Vulliamy T.J., Luzzatto L.;
RT "G6PD Aures: a new mutation (48 Ile-->Thr) causing mild G6PD
RT deficiency is associated with favism.";
RL Hum. Mol. Genet. 2:81-82(1993).
RN [38]
RP VARIANT SHINSHU GLY-176.
RX PubMed=8193373;
RA Hirono A., Miwa S., Fujii H., Ishida F., Yamada K., Kubota K.;
RT "Molecular study of eight Japanese cases of glucose-6-phosphate
RT dehydrogenase deficiency by nonradioisotopic single-strand
RT conformation polymorphism analysis.";
RL Blood 83:3363-3368(1994).
RN [39]
RP VARIANT BARI LEU-396.
RX PubMed=7959695; DOI=10.1007/BF00211027;
RA Filosa S., Cai W., Galanello R., Cao A., de Mattia D., Schettini F.,
RA Martini G.;
RT "A novel single-base mutation in the glucose 6-phosphate dehydrogenase
RT gene is associated with chronic non-spherocytic haemolytic anaemia.";
RL Hum. Genet. 94:560-562(1994).
RN [40]
RP VARIANTS NAMORU; VANUA LAVA; NAONE AND UNION.
RX PubMed=7825590;
RA Ganczakowski M., Town M., Bowden D.K., Vulliamy T.J., Kaneko A.,
RA Clegg J.B., Weatherall D.J., Luzzatto L.;
RT "Multiple glucose 6-phosphate dehydrogenase-deficient variants
RT correlate with malaria endemicity in the Vanuatu archipelago
RT (southwestern Pacific).";
RL Am. J. Hum. Genet. 56:294-301(1995).
RN [41]
RP VARIANT ORISSA GLY-44.
RX PubMed=8533762;
RA Kaeda J.S., Chhotray G.P., Ranjit M.R., Bautista J.M., Reddy P.H.,
RA Stevens D., Naidu J.M., Britt R.P., Vulliamy T.J., Luzzatto L.,
RA Mason P.J.;
RT "A new glucose-6-phosphate dehydrogenase variant, G6PD Orissa (44
RT Ala-->Gly), is the major polymorphic variant in tribal populations in
RT India.";
RL Am. J. Hum. Genet. 57:1335-1341(1995).
RN [42]
RP VARIANTS SWANSEA PRO-75; PLYMOUTH ASP-163; CORUM LYS-274 AND WEXHAM
RP PHE-278.
RX PubMed=7858267;
RA Mason P.J., Sonati M.F., Macdonald D., Lanza C., Busutil D., Town M.,
RA Corcoran C.M., Kaeda J.S., Stevens D.J., Al-Ismail S., Altay C.,
RA Hatton C., Lewis D.S., McMullin M.F., Meloni T., Paul B., Pippard M.,
RA Prentice A.G., Vulliamy T.J., Luzzatto L.;
RT "New glucose-6-phosphate dehydrogenase mutations associated with
RT chronic anemia.";
RL Blood 85:1377-1380(1995).
RN [43]
RP VARIANTS MOUNT SINAI ASP-126 AND CYS-387.
RX PubMed=9452072;
RA Vlachos A., Westwood B., Lipton J.M., Beutler E.;
RT "G6PD Mount Sinai: a new severe hemolytic variant characterized by
RT dual mutations at nucleotides 376G and 1159T (N126D).";
RL Hum. Mutat. Suppl. 1:S154-S155(1998).
RN [44]
RP VARIANT SINNAI LEU-12.
RX PubMed=10627140;
RX DOI=10.1002/(SICI)1098-1004(1998)12:1<72::AID-HUMU19>3.3.CO;2-K;
RA Galanello R., Loi D., Sollaino C., Dessi S., Cao A., Melis M.A.;
RT "A new glucose 6 phosphate dehydrogenase variant, G6PD Sinnai (34
RT G->T).";
RL Hum. Mutat. 12:72-73(1998).
RN [45]
RP VARIANT REHOVOT HIS-322.
RX PubMed=11112389; DOI=10.1006/bcmd.2000.0334;
RA Iancovici-Kidon M., Sthoeger D., Abrahamov A., Volach B., Beutler E.,
RA Gelbart T., Barak Y.;
RT "A new exon 9 glucose-6-phosphate dehydrogenase mutation (G6PD
RT 'Rehovot') in a Jewish Ethiopian family with variable phenotypes.";
RL Blood Cells Mol. Dis. 26:567-571(2000).
RN [46]
RP ASSOCIATION OF VARIANT MAHIDOL SER-163 WITH REDUCED DENSITY OF
RP PLASMODIUM VIVAX.
RX PubMed=20007901; DOI=10.1126/science.1178849;
RA Louicharoen C., Patin E., Paul R., Nuchprayoon I., Witoonpanich B.,
RA Peerapittayamongkol C., Casademont I., Sura T., Laird N.M.,
RA Singhasivanon P., Quintana-Murci L., Sakuntabhai A.;
RT "Positively selected G6PD-Mahidol mutation reduces Plasmodium vivax
RT density in Southeast Asians.";
RL Science 326:1546-1549(2009).
CC -!- FUNCTION: Catalyzes the rate-limiting step of the oxidative
CC pentose-phosphate pathway, which represents a route for the
CC dissimilation of carbohydrates besides glycolysis. The main
CC function of this enzyme is to provide reducing power (NADPH) and
CC pentose phosphates for fatty acid and nucleic acid synthesis.
CC -!- CATALYTIC ACTIVITY: D-glucose 6-phosphate + NADP(+) = 6-phospho-D-
CC glucono-1,5-lactone + NADPH.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=7.07 uM for NADP;
CC KM=52 uM for glucose 6-phosphate;
CC -!- PATHWAY: Carbohydrate degradation; pentose phosphate pathway; D-
CC ribulose 5-phosphate from D-glucose 6-phosphate (oxidative stage):
CC step 1/3.
CC -!- SUBUNIT: Homotetramer; dimer of dimers.
CC -!- INTERACTION:
CC P04792:HSPB1; NbExp=2; IntAct=EBI-4289891, EBI-352682;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=Short;
CC IsoId=P11413-1; Sequence=Displayed;
CC Name=Long;
CC IsoId=P11413-2; Sequence=VSP_001592;
CC Name=3;
CC IsoId=P11413-3; Sequence=VSP_037802;
CC Note=Contains a phosphoserine at position 26;
CC -!- TISSUE SPECIFICITY: Isoform Long is found in lymphoblasts,
CC granulocytes and sperm.
CC -!- POLYMORPHISM: The sequence shown is that of variant B, the most
CC common variant.
CC -!- DISEASE: Anemia, non-spherocytic hemolytic, due to G6PD deficiency
CC (NSHA) [MIM:300908]: A disease characterized by G6PD deficiency,
CC acute hemolytic anemia, fatigue, back pain, and jaundice. In most
CC patients, the disease is triggered by an exogenous agent, such as
CC some drugs, food, or infection. Increased unconjugated bilirubin,
CC lactate dehydrogenase, and reticulocytosis are markers of the
CC disorder. Although G6PD deficiency can be life-threatening, most
CC patients are asymptomatic throughout their life. Note=The disease
CC is caused by mutations affecting the gene represented in this
CC entry. Deficiency of G6PD is associated with hemolytic anemia in
CC two different situations. First, in areas in which malaria has
CC been endemic, G6PD-deficiency alleles have reached high
CC frequencies (1% to 50%) and deficient individuals, though
CC essentially asymptomatic in the steady state, have a high risk of
CC acute hemolytic attacks. Secondly, sporadic cases of G6PD
CC deficiency occur at a very low frequencies, and they usually
CC present a more severe phenotype. Several types of NSHA are
CC recognized. Class-I variants are associated with severe NSHA;
CC class-II have an activity <10% of normal; class-III have an
CC activity of 10% to 60% of normal; class-IV have near normal
CC activity.
CC -!- MISCELLANEOUS: Binds two molecules of NADP. The first one is a
CC cosubstrate (bound to the N-terminal domain), the second is bound
CC to the C-terminal domain and functions as a structural element.
CC -!- SIMILARITY: Belongs to the glucose-6-phosphate dehydrogenase
CC family.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA63175.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC -!- WEB RESOURCE: Name=G6PD; Note=G6PD deficiency resource;
CC URL="http://rialto.com/g6pd/";
CC -!- WEB RESOURCE: Name=G6PDdb; Note=G6PD mutation database;
CC URL="http://www.bioinf.org.uk/g6pd/";
CC -!- WEB RESOURCE: Name=GeneReviews;
CC URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/G6PD";
CC -!- WEB RESOURCE: Name=SHMPD; Note=The Singapore human mutation and
CC polymorphism database;
CC URL="http://shmpd.bii.a-star.edu.sg/gene.php?genestart=A&genename;=G6PD";
CC -----------------------------------------------------------------------
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DR EMBL; X03674; CAA27309.1; -; mRNA.
DR EMBL; M65234; AAA63175.1; ALT_INIT; Genomic_DNA.
DR EMBL; M26749; AAA63175.1; JOINED; Genomic_DNA.
DR EMBL; M26750; AAA63175.1; JOINED; Genomic_DNA.
DR EMBL; M65225; AAA63175.1; JOINED; Genomic_DNA.
DR EMBL; M65226; AAA63175.1; JOINED; Genomic_DNA.
DR EMBL; M65227; AAA63175.1; JOINED; Genomic_DNA.
DR EMBL; M65228; AAA63175.1; JOINED; Genomic_DNA.
DR EMBL; M65229; AAA63175.1; JOINED; Genomic_DNA.
DR EMBL; M65230; AAA63175.1; JOINED; Genomic_DNA.
DR EMBL; M65231; AAA63175.1; JOINED; Genomic_DNA.
DR EMBL; M65233; AAA63175.1; JOINED; Genomic_DNA.
DR EMBL; M65232; AAA63175.1; JOINED; Genomic_DNA.
DR EMBL; M21248; AAA52500.1; -; mRNA.
DR EMBL; M19866; AAA52501.1; -; mRNA.
DR EMBL; X55448; CAA39089.1; -; Genomic_DNA.
DR EMBL; L44140; AAA92653.1; -; Genomic_DNA.
DR EMBL; AF277315; AAL27011.1; -; Genomic_DNA.
DR EMBL; CH471172; EAW72682.1; -; Genomic_DNA.
DR EMBL; CH471172; EAW72686.1; -; Genomic_DNA.
DR EMBL; BC000337; AAH00337.1; -; mRNA.
DR EMBL; M27940; AAA52504.1; -; mRNA.
DR EMBL; S58359; AAB26169.1; -; mRNA.
DR EMBL; X53815; CAA37811.1; -; Genomic_DNA.
DR EMBL; S64462; AAB20299.1; -; Genomic_DNA.
DR EMBL; AY158096; AAN76367.1; -; Genomic_DNA.
DR EMBL; AY158097; AAN76368.1; -; Genomic_DNA.
DR EMBL; AY158098; AAN76369.1; -; Genomic_DNA.
DR EMBL; AY158099; AAN76370.1; -; Genomic_DNA.
DR EMBL; AY158100; AAN76371.1; -; Genomic_DNA.
DR EMBL; AY158101; AAN76372.1; -; Genomic_DNA.
DR EMBL; AY158102; AAN76373.1; -; Genomic_DNA.
DR EMBL; AY158103; AAN76374.1; -; Genomic_DNA.
DR EMBL; AY158104; AAN76375.1; -; Genomic_DNA.
DR EMBL; AY158105; AAN76376.1; -; Genomic_DNA.
DR EMBL; AY158106; AAN76377.1; -; Genomic_DNA.
DR EMBL; AY158107; AAN76378.1; -; Genomic_DNA.
DR EMBL; AY158108; AAN76379.1; -; Genomic_DNA.
DR EMBL; AY158109; AAN76380.1; -; Genomic_DNA.
DR EMBL; AY158110; AAN76381.1; -; Genomic_DNA.
DR EMBL; AY158111; AAN76382.1; -; Genomic_DNA.
DR EMBL; AY158112; AAN76383.1; -; Genomic_DNA.
DR EMBL; AY158113; AAN76384.1; -; Genomic_DNA.
DR EMBL; AY158114; AAN76385.1; -; Genomic_DNA.
DR EMBL; AY158115; AAN76386.1; -; Genomic_DNA.
DR EMBL; AY158116; AAN76387.1; -; Genomic_DNA.
DR EMBL; AY158117; AAN76388.1; -; Genomic_DNA.
DR EMBL; AY158118; AAN76389.1; -; Genomic_DNA.
DR EMBL; AY158119; AAN76390.1; -; Genomic_DNA.
DR EMBL; AY158120; AAN76391.1; -; Genomic_DNA.
DR EMBL; AY158121; AAN76392.1; -; Genomic_DNA.
DR EMBL; AY158122; AAN76393.1; -; Genomic_DNA.
DR EMBL; AY158123; AAN76394.1; -; Genomic_DNA.
DR EMBL; AY158124; AAN76395.1; -; Genomic_DNA.
DR EMBL; AY158125; AAN76396.1; -; Genomic_DNA.
DR EMBL; AY158126; AAN76397.1; -; Genomic_DNA.
DR EMBL; AY158127; AAN76398.1; -; Genomic_DNA.
DR EMBL; AY158128; AAN76399.1; -; Genomic_DNA.
DR EMBL; AY158129; AAN76400.1; -; Genomic_DNA.
DR EMBL; AY158130; AAN76401.1; -; Genomic_DNA.
DR EMBL; AY158131; AAN76402.1; -; Genomic_DNA.
DR EMBL; AY158132; AAN76403.1; -; Genomic_DNA.
DR EMBL; AY158133; AAN76404.1; -; Genomic_DNA.
DR EMBL; AY158134; AAN76405.1; -; Genomic_DNA.
DR EMBL; AY158135; AAN76406.1; -; Genomic_DNA.
DR EMBL; AY158136; AAN76407.1; -; Genomic_DNA.
DR EMBL; AY158137; AAN76408.1; -; Genomic_DNA.
DR EMBL; AY158138; AAN76409.1; -; Genomic_DNA.
DR EMBL; AY158139; AAN76410.1; -; Genomic_DNA.
DR EMBL; AY158140; AAN76411.1; -; Genomic_DNA.
DR EMBL; AY158141; AAN76412.1; -; Genomic_DNA.
DR EMBL; AY158142; AAN76413.1; -; Genomic_DNA.
DR EMBL; M12996; AAA52499.1; -; mRNA.
DR EMBL; M23423; AAB59390.1; -; Genomic_DNA.
DR PIR; A40309; DEHUG6.
DR RefSeq; NP_000393.4; NM_000402.4.
DR RefSeq; NP_001035810.1; NM_001042351.2.
DR UniGene; Hs.461047; -.
DR UniGene; Hs.684904; -.
DR PDB; 1QKI; X-ray; 3.00 A; A/B/C/D/E/F/G/H=2-515.
DR PDB; 2BH9; X-ray; 2.50 A; A=28-514.
DR PDB; 2BHL; X-ray; 2.90 A; A/B=28-515.
DR PDBsum; 1QKI; -.
DR PDBsum; 2BH9; -.
DR PDBsum; 2BHL; -.
DR ProteinModelPortal; P11413; -.
DR SMR; P11413; 28-515.
DR IntAct; P11413; 2.
DR MINT; MINT-4716941; -.
DR STRING; 9606.ENSP00000377192; -.
DR BindingDB; P11413; -.
DR ChEMBL; CHEMBL5347; -.
DR PhosphoSite; P11413; -.
DR DMDM; 116242483; -.
DR REPRODUCTION-2DPAGE; IPI00289800; -.
DR SWISS-2DPAGE; P11413; -.
DR PaxDb; P11413; -.
DR PRIDE; P11413; -.
DR DNASU; 2539; -.
DR Ensembl; ENST00000369620; ENSP00000358633; ENSG00000160211.
DR Ensembl; ENST00000393562; ENSP00000377192; ENSG00000160211.
DR Ensembl; ENST00000393564; ENSP00000377194; ENSG00000160211.
DR Ensembl; ENST00000593787; ENSP00000471208; ENSG00000269087.
DR Ensembl; ENST00000594771; ENSP00000470721; ENSG00000269087.
DR Ensembl; ENST00000595441; ENSP00000469988; ENSG00000269087.
DR GeneID; 2539; -.
DR KEGG; hsa:2539; -.
DR UCSC; uc004fly.1; human.
DR CTD; 2539; -.
DR GeneCards; GC0XM153759; -.
DR HGNC; HGNC:4057; G6PD.
DR HPA; HPA000247; -.
DR HPA; HPA000834; -.
DR MIM; 300908; phenotype.
DR MIM; 305900; gene.
DR neXtProt; NX_P11413; -.
DR Orphanet; 362; Glucose-6-phosphate-dehydrogenase deficiency.
DR PharmGKB; PA28469; -.
DR eggNOG; COG0364; -.
DR HOVERGEN; HBG000856; -.
DR KO; K00036; -.
DR OMA; AVVFKRA; -.
DR Reactome; REACT_111217; Metabolism.
DR SABIO-RK; P11413; -.
DR UniPathway; UPA00115; UER00408.
DR ChiTaRS; G6PD; human.
DR EvolutionaryTrace; P11413; -.
DR GeneWiki; Glucose-6-phosphate_dehydrogenase; -.
DR GenomeRNAi; 2539; -.
DR NextBio; 10021; -.
DR PRO; PR:P11413; -.
DR ArrayExpress; P11413; -.
DR Bgee; P11413; -.
DR CleanEx; HS_G6PD; -.
DR Genevestigator; P11413; -.
DR GO; GO:0005813; C:centrosome; IDA:HPA.
DR GO; GO:0009898; C:cytoplasmic side of plasma membrane; IDA:BHF-UCL.
DR GO; GO:0005829; C:cytosol; IDA:BHF-UCL.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IEA:Ensembl.
DR GO; GO:0005536; F:glucose binding; IDA:BHF-UCL.
DR GO; GO:0004345; F:glucose-6-phosphate dehydrogenase activity; IDA:UniProtKB.
DR GO; GO:0050661; F:NADP binding; IDA:BHF-UCL.
DR GO; GO:0034599; P:cellular response to oxidative stress; IMP:BHF-UCL.
DR GO; GO:0006695; P:cholesterol biosynthetic process; IMP:BHF-UCL.
DR GO; GO:0001816; P:cytokine production; IMP:BHF-UCL.
DR GO; GO:0043249; P:erythrocyte maturation; IMP:BHF-UCL.
DR GO; GO:0051156; P:glucose 6-phosphate metabolic process; IDA:UniProtKB.
DR GO; GO:0006749; P:glutathione metabolic process; IMP:BHF-UCL.
DR GO; GO:0010734; P:negative regulation of protein glutathionylation; IMP:BHF-UCL.
DR GO; GO:0019322; P:pentose biosynthetic process; IDA:BHF-UCL.
DR GO; GO:0009051; P:pentose-phosphate shunt, oxidative branch; IMP:BHF-UCL.
DR GO; GO:0045471; P:response to ethanol; IEA:Ensembl.
DR GO; GO:0032094; P:response to food; IEA:Ensembl.
DR GO; GO:0014070; P:response to organic cyclic compound; IEA:Ensembl.
DR GO; GO:0046390; P:ribose phosphate biosynthetic process; IMP:BHF-UCL.
DR Gene3D; 3.40.50.720; -; 1.
DR HAMAP; MF_00966; G6PD; 1; -.
DR InterPro; IPR001282; G6P_DH.
DR InterPro; IPR019796; G6P_DH_AS.
DR InterPro; IPR022675; G6P_DH_C.
DR InterPro; IPR022674; G6P_DH_NAD-bd.
DR InterPro; IPR016040; NAD(P)-bd_dom.
DR PANTHER; PTHR23429; PTHR23429; 1.
DR Pfam; PF02781; G6PD_C; 1.
DR Pfam; PF00479; G6PD_N; 1.
DR PIRSF; PIRSF000110; G6PD; 1.
DR PRINTS; PR00079; G6PDHDRGNASE.
DR TIGRFAMs; TIGR00871; zwf; 1.
DR PROSITE; PS00069; G6P_DEHYDROGENASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing;
KW Carbohydrate metabolism; Complete proteome; Direct protein sequencing;
KW Disease mutation; Glucose metabolism; Hereditary hemolytic anemia;
KW NADP; Oxidoreductase; Phosphoprotein; Polymorphism;
KW Reference proteome.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 515 Glucose-6-phosphate 1-dehydrogenase.
FT /FTId=PRO_0000068083.
FT NP_BIND 38 45 NADP 1.
FT NP_BIND 401 403 NADP 2.
FT NP_BIND 421 423 NADP 2.
FT REGION 201 205 Substrate binding.
FT ACT_SITE 263 263 Proton acceptor (By similarity).
FT BINDING 72 72 NADP 1.
FT BINDING 147 147 NADP 1.
FT BINDING 171 171 NADP 1; via carbonyl oxygen.
FT BINDING 171 171 Substrate.
FT BINDING 239 239 Substrate.
FT BINDING 258 258 Substrate.
FT BINDING 357 357 NADP 2.
FT BINDING 360 360 Substrate.
FT BINDING 365 365 Substrate.
FT BINDING 366 366 NADP 2.
FT BINDING 370 370 NADP 2.
FT BINDING 393 393 NADP 2.
FT BINDING 395 395 Substrate.
FT BINDING 487 487 NADP 2.
FT BINDING 503 503 NADP 2.
FT BINDING 509 509 NADP 2.
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 89 89 N6-acetyllysine.
FT MOD_RES 171 171 N6-acetyllysine.
FT MOD_RES 403 403 N6-acetyllysine.
FT MOD_RES 432 432 N6-acetyllysine.
FT MOD_RES 497 497 N6-acetyllysine.
FT VAR_SEQ 1 1 M -> MGRRGSAPGNGRTLRGCERGGRRRRSADSVM (in
FT isoform 3).
FT /FTId=VSP_037802.
FT VAR_SEQ 257 257 R -> RGPGRQGGSGSESCSLSLGSLVWGPHALEPGEQGGE
FT LRRALASSVPR (in isoform Long).
FT /FTId=VSP_001592.
FT VARIANT 12 12 V -> L (in Sinnai).
FT /FTId=VAR_002450.
FT VARIANT 32 32 H -> R (in CSNA; Gahoe; class III;
FT frequent in Chinese).
FT /FTId=VAR_002451.
FT VARIANT 35 35 Missing (in NSHA; Sunderland; class I).
FT /FTId=VAR_002452.
FT VARIANT 44 44 A -> G (in Orissa; class III; frequent in
FT Indian tribal populations).
FT /FTId=VAR_002453.
FT VARIANT 48 48 I -> T (in Aures; class II).
FT /FTId=VAR_002454.
FT VARIANT 58 58 D -> N (in Metaponto; class III).
FT /FTId=VAR_002455.
FT VARIANT 68 68 V -> M (in A(-) type I; class III;
FT frequent in African population;
FT dbSNP:rs1050828).
FT /FTId=VAR_002456.
FT VARIANT 70 70 Y -> H (in Namoru; 4% activity).
FT /FTId=VAR_002457.
FT VARIANT 75 75 L -> P (in Swansea; class I).
FT /FTId=VAR_002458.
FT VARIANT 81 81 R -> C (in Konan/Ube; class III;
FT dbSNP:rs138687036).
FT /FTId=VAR_002460.
FT VARIANT 81 81 R -> H (in Lagosanto; class III).
FT /FTId=VAR_002459.
FT VARIANT 106 106 S -> C (in Vancouver; class I).
FT /FTId=VAR_002461.
FT VARIANT 126 126 N -> D (in A(+), A(-), Santa Maria; class
FT IV and in Mount Sinai; class I;
FT dbSNP:rs1050829).
FT /FTId=VAR_002462.
FT VARIANT 128 128 L -> P (in Vanua Lava; 4% activity).
FT /FTId=VAR_002463.
FT VARIANT 131 131 G -> V (in Chinese-4; dbSNP:rs137852341).
FT /FTId=VAR_002464.
FT VARIANT 156 156 E -> K (in Ilesha; class III).
FT /FTId=VAR_002465.
FT VARIANT 163 163 G -> D (in Plymouth; class I).
FT /FTId=VAR_002467.
FT VARIANT 163 163 G -> S (in Mahidol; class III; reduced
FT activity; associated with reduced density
FT of Plasmodium vivax but not Plasmodium
FT falciparum in Southeast Asians).
FT /FTId=VAR_002466.
FT VARIANT 165 165 N -> D (in Chinese-3; class II).
FT /FTId=VAR_002468.
FT VARIANT 166 166 R -> H (in Naone; 1% activity).
FT /FTId=VAR_002469.
FT VARIANT 176 176 D -> G (in Shinshu; class I).
FT /FTId=VAR_002470.
FT VARIANT 181 181 D -> V (in Santa Maria; class I;
FT dbSNP:rs5030872).
FT /FTId=VAR_002471.
FT VARIANT 182 182 R -> W (in Vancouver; class I).
FT /FTId=VAR_002472.
FT VARIANT 188 188 S -> F (in Sassari/Cagliari; class II;
FT frequent in the Mediterranean;
FT dbSNP:rs5030868).
FT /FTId=VAR_002473.
FT VARIANT 198 198 R -> C (in Coimbra; class II).
FT /FTId=VAR_002474.
FT VARIANT 198 198 R -> P (in NSHA; Santiago; class I).
FT /FTId=VAR_002475.
FT VARIANT 212 212 M -> V (in Sibari; class III).
FT /FTId=VAR_002476.
FT VARIANT 213 213 V -> L (in Minnesota; class I).
FT /FTId=VAR_002477.
FT VARIANT 216 216 F -> L (in Harilaou; class I).
FT /FTId=VAR_002478.
FT VARIANT 227 227 R -> L (in A- type 2; class III).
FT /FTId=VAR_002480.
FT VARIANT 227 227 R -> Q (in Mexico City; class III).
FT /FTId=VAR_002479.
FT VARIANT 242 243 Missing (in Stonybrook; class I).
FT /FTId=VAR_002481.
FT VARIANT 257 257 R -> G (in Wayne; class I).
FT /FTId=VAR_002482.
FT VARIANT 274 274 E -> K (in Corum; class I).
FT /FTId=VAR_002483.
FT VARIANT 278 278 S -> F (in Wexham; class I).
FT /FTId=VAR_002484.
FT VARIANT 279 279 T -> S (in Chinese-1; class II).
FT /FTId=VAR_002485.
FT VARIANT 282 282 D -> H (in Seattle; class III).
FT /FTId=VAR_002486.
FT VARIANT 285 285 R -> H (in Montalbano; class III).
FT /FTId=VAR_002487.
FT VARIANT 291 291 V -> M (in Viangchan/Jammu; class II).
FT /FTId=VAR_002488.
FT VARIANT 317 317 E -> K (in Kalyan/Kerala; class III).
FT /FTId=VAR_002489.
FT VARIANT 322 322 Y -> H (in Rehovot).
FT /FTId=VAR_020535.
FT VARIANT 323 323 L -> P (in A- type 3; class III;
FT dbSNP:rs76723693).
FT /FTId=VAR_002490.
FT VARIANT 335 335 A -> T (in Chatham; class III;
FT dbSNP:rs5030869).
FT /FTId=VAR_002491.
FT VARIANT 342 342 L -> F (in Chinese-5).
FT /FTId=VAR_002492.
FT VARIANT 353 353 P -> S (in Ierapetra; class II).
FT /FTId=VAR_002493.
FT VARIANT 363 363 N -> K (in Loma Linda; class I).
FT /FTId=VAR_002494.
FT VARIANT 385 385 C -> R (in Tomah; class I).
FT /FTId=VAR_002495.
FT VARIANT 386 386 K -> E (in Iowa; class I).
FT /FTId=VAR_002496.
FT VARIANT 387 387 R -> C (in NSHA; Guadajalara and Mount
FT Sinai; class I).
FT /FTId=VAR_002498.
FT VARIANT 387 387 R -> H (in Beverly Hills; class I).
FT /FTId=VAR_002497.
FT VARIANT 393 393 R -> H (in Nashville/Anaheim; class I).
FT /FTId=VAR_002499.
FT VARIANT 394 394 V -> L (in NSHA; Alhambra; class I).
FT /FTId=VAR_002500.
FT VARIANT 396 396 P -> L (in Bari; class I).
FT /FTId=VAR_002501.
FT VARIANT 398 398 E -> K (in Puerto Limon; class I).
FT /FTId=VAR_002502.
FT VARIANT 410 410 G -> C (in Riverside; class I).
FT /FTId=VAR_002503.
FT VARIANT 410 410 G -> D (in NSHA; Japan; class I).
FT /FTId=VAR_002504.
FT VARIANT 416 416 E -> K (in Tokyo; class I).
FT /FTId=VAR_002505.
FT VARIANT 439 439 R -> P (in NSHA; Pawnee; class I).
FT /FTId=VAR_002506.
FT VARIANT 440 440 L -> F (in Telti/Kobe; class I).
FT /FTId=VAR_002507.
FT VARIANT 447 447 G -> R (in Santiago de Cuba; class I).
FT /FTId=VAR_002508.
FT VARIANT 449 449 Q -> H (in Cassano; class II).
FT /FTId=VAR_002509.
FT VARIANT 454 454 R -> C (in Chinese-II/Maewo/Union; class
FT II, <1% activity).
FT /FTId=VAR_002510.
FT VARIANT 454 454 R -> H (in Andalus; class I).
FT /FTId=VAR_002511.
FT VARIANT 459 459 R -> L (in Canton; class II; frequent in
FT China; dbSNP:rs72554665).
FT /FTId=VAR_002512.
FT VARIANT 459 459 R -> P (in Cosenza; class II;
FT dbSNP:rs72554665).
FT /FTId=VAR_002513.
FT VARIANT 463 463 R -> H (in Kaiping; class II).
FT /FTId=VAR_002514.
FT VARIANT 488 488 G -> V (in Campinas; class I).
FT /FTId=VAR_002515.
FT CONFLICT 11 11 Q -> H (in Ref. 1; CAA27309, 2; AAA63175
FT and 3; AAA52500).
FT CONFLICT 435 436 DA -> EP (in Ref. 15; AAA52499).
FT STRAND 32 37
FT TURN 38 40
FT HELIX 42 46
FT HELIX 48 57
FT STRAND 63 73
FT HELIX 77 84
FT HELIX 85 87
FT HELIX 92 94
FT HELIX 95 103
FT STRAND 105 109
FT HELIX 115 126
FT TURN 127 133
FT STRAND 134 140
FT TURN 144 146
FT HELIX 147 157
FT STRAND 161 163
FT STRAND 165 169
FT HELIX 177 187
FT TURN 188 190
FT HELIX 193 195
FT STRAND 196 198
FT HELIX 201 204
FT HELIX 206 216
FT HELIX 219 221
FT STRAND 222 226
FT TURN 227 229
FT STRAND 230 238
FT HELIX 247 250
FT TURN 251 253
FT HELIX 254 258
FT TURN 259 262
FT HELIX 263 272
FT STRAND 277 280
FT HELIX 281 292
FT HELIX 300 302
FT STRAND 303 309
FT HELIX 317 319
FT HELIX 322 324
FT STRAND 326 328
FT STRAND 336 344
FT TURN 347 351
FT STRAND 353 361
FT STRAND 366 373
FT STRAND 389 397
FT STRAND 399 407
FT TURN 409 411
FT STRAND 414 423
FT TURN 424 426
FT STRAND 427 431
FT HELIX 436 446
FT HELIX 449 451
FT HELIX 455 475
FT STRAND 480 483
FT STRAND 486 488
FT HELIX 490 498
SQ SEQUENCE 515 AA; 59257 MW; F2B775340640A96F CRC64;
MAEQVALSRT QVCGILREEL FQGDAFHQSD THIFIIMGAS GDLAKKKIYP TIWWLFRDGL
LPENTFIVGY ARSRLTVADI RKQSEPFFKA TPEEKLKLED FFARNSYVAG QYDDAASYQR
LNSHMNALHL GSQANRLFYL ALPPTVYEAV TKNIHESCMS QIGWNRIIVE KPFGRDLQSS
DRLSNHISSL FREDQIYRID HYLGKEMVQN LMVLRFANRI FGPIWNRDNI ACVILTFKEP
FGTEGRGGYF DEFGIIRDVM QNHLLQMLCL VAMEKPASTN SDDVRDEKVK VLKCISEVQA
NNVVLGQYVG NPDGEGEATK GYLDDPTVPR GSTTATFAAV VLYVENERWD GVPFILRCGK
ALNERKAEVR LQFHDVAGDI FHQQCKRNEL VIRVQPNEAV YTKMMTKKPG MFFNPEESEL
DLTYGNRYKN VKLPDAYERL ILDVFCGSQM HFVRSDELRE AWRIFTPLLH QIELEKPKPI
PYIYGSRGPT EADELMKRVG FQYEGTYKWV NPHKL
//

MIM 300908
*RECORD*
*FIELD* NO
300908
*FIELD* TI
#300908 ANEMIA, NONSPHEROCYTIC HEMOLYTIC, DUE TO G6PD DEFICIENCY
*FIELD* TX
A number sign (#) is used with this entry because this form of
read morenonspherocytic hemolyic anemia is caused by mutation in the G6PD gene
(305900) on chromosome Xq28.

DESCRIPTION

G6PD deficiency is the most common genetic cause of chronic and drug-,
food-, or infection-induced hemolytic anemia. G6PD catalyzes the first
reaction in the pentose phosphate pathway, which is the only
NADPH-generation process in mature red cells; therefore, defense against
oxidative damage is dependent on G6PD. The most common clinical
manifestations of G6PD deficiency are neonatal jaundice and acute
hemolytic anemia, which in most patients is triggered by an exogenous
agent, e.g., primaquine or fava beans (see 134700). Acute hemolysis is
characterized by fatigue, back pain, anemia, and jaundice. Increased
unconjugated bilirubin, lactate dehydrogenase, and reticulocytosis are
markers of the disorder. Although G6PD deficiency can be
life-threatening, most G6PD-deficient patients are asymptomatic
throughout their life. The striking similarity between the areas where
G6PD deficiency is common and Plasmodium falciparum malaria (see 611162)
is endemic provided evidence that G6PD deficiency confers resistance
against malaria (summary by Cappellini and Fiorelli, 2008).

CLINICAL FEATURES

In primiquine-sensitive patients with hemolytic anemia, Carson et al.
(1956) demonstrated an abnormality in the direct oxidation of glucose in
red blood cells and deficiency of glucose-6-phosphate dehydrogenase.

Cooper et al. (1972) and Gray et al. (1973) found that complete
deficiency of G6PD produces not only nonspherocytic hemolytic anemia but
also chronic granulomatous disease due to neutrophil dysfunction. The
patient of Cooper et al. (1972) was a woman with complete leukocyte G6PD
deficiency, partial deficiency in her red cells, and no family history
of G6PD deficiency. Of the various possible explanations advanced by the
authors, they preferred the suggestion that X-inactivation had affected
the red cell and white cell series differently and that the patient
indeed had G6PD deficiency. Gray et al. (1973) described 3 affected
brothers. The mother showed an intermediate defect in leukocyte
microbicidal and metabolic activity, as well as red and white blood cell
mosaicism.

In Saudi Arabia, Mallouh and Abu-Osba (1987) reviewed the G6PD status of
all children aged 1 month to 14 years who were treated for meningitis,
septicemia, osteomyelitis, or typhoid fever during a 9-year period. The
observed frequency of G6PD deficiency was significantly higher than
expected for the entire group, for females with both catalase-positive
and catalase-negative infection, and for males with catalase-positive
infections.

Zinkham (1961) found that individuals with primaquine-sensitive
erythrocytes had deficiency of G6PD activity in the lens. Orzalesi et
al. (1981) found that G6PD deficiency was significantly more frequent
among 210 male cataract patients in Sardinia than in 672 control
subjects. This was particularly the case with presenile cataracts. Also
in Sardinia, however, Meloni et al. (1990) found that patients with
cataract had frequencies of G6PD deficiency no different from those in
the general population.

Ferraris et al. (1988) examined the hypothesis that there is a negative
correlation between G6PD deficiency and hematologic malignancy. The
frequency of G6PD deficiency in 481 Sardinian males with hematologic
malignancies was not significantly different from that in a group of
16,219 controls. Similarly, no differences were found in the frequency
of expression of the Gd(B) gene in women with clonal hematologic
disorders and healthy heterozygotes. There was no evidence that G6PD
provides a protective effect against the development of hematologic
malignancy.

Beutler (1994) pointed out that 35 years previously William Demeshek,
the first editor of the emerging journal 'Blood,' had invited him to
write a review on 'The Hemolytic Effect of Primaquine and Related
Compounds' (Beutler, 1959). Beutler (1994) attempted to put into
perspective what had been learned in the 35-year interval and to touch
upon what still needed to be learned. He provided a comprehensive
tabulation of those G6PD variants that had been characterized at the DNA
level as well as information on the population distribution of common
G6PD mutations. He pointed out that the most dangerous consequence of
G6PD deficiency is neonatal icterus. Kernicterus has been documented
repeatedly in populations in which class 2 variants are common and is an
important preventable form of mental retardation. Phototherapy has been
used to reduce bilirubin levels and phenobarbital has been used
prophylactically with some success. Exchange transfusion is required if
the bilirubin exceeds 20 mg/dL.

Ninfali et al. (1995) studied muscle expression of G6PD in normal
individuals and in persons with G6PD deficiency of 3 types. They were
prompted to undertake these studies because of patients with symptoms
such as myalgia, cramps, and muscle weakness under conditions of stress,
particularly physical exertion. All 3 variants--Mediterranean
(305900.0006), Seattle-like (305900.0010), and G6PD A-
(305900.0002)--showed the enzyme defect in muscle. A statistically
significant relationship was found in the activity of G6PD in
erythrocytes and muscle of male subjects. The results suggested to the
authors that, for a given variant, the extent of the enzyme defect in
muscle can be determined from the G6PD activity of erythrocytes, using
an equation that they derived.

That resistance to severe malaria (see 611162) is the basis of the high
frequency of G6PD deficiency and that both hemizygotes and heterozygotes
enjoy an advantage was established by Ruwando et al. (1995) in 2 large
case-control studies of more than 2,000 African children. They found
that the common African form of G6PD deficiency (G6PD A-; 305900.0002)
was associated with a 46 to 58% reduction in risk of severe malaria for
both female heterozygotes and male hemizygotes. A mathematical model
incorporating the measured selective advantage against malaria suggested
that a counterbalancing selective disadvantage, associated with this
enzyme deficiency, has retarded its rise in frequency in malaria-endemic
regions.

Cocco et al. (1998) reported a mortality study of a cohort of 1,756 men
with G6PD deficiency identified during a 1981 population screening in
Sardinia and followed during the period January 1, 1982 through December
31, 1992. Outcome measures were cause-specific standardized mortality
ratios (SMRs), which were computed as 100 times the observed/expected
ratio, with the general Sardinian male population as the reference.
Deaths from all causes were significantly less than expected due to
decreased SMRs for ischemic heart disease, cerebrovascular disease, and
liver cirrhosis, which explained 95.6% of the deficit in total
mortality. All cancer mortality was close to the expectation, with a
significant increase in the SMR for non-Hodgkin lymphoma. Increased
mortality from non-Hodgkin lymphoma and decrease in mortality from liver
cirrhosis were new observations. Decrease in mortality from
cardiovascular disease may have been based on selection bias because the
population screening was not random but was based on volunteers, who may
have been more concerned than the average about their health.

In comparison with normal neonates, G6PD-deficient neonates experience a
2-fold increase in the prevalence of significant hyperbilirubinemia
requiring phototherapy. Kappas et al. (2001) tested the efficacy of a
single dose of intramuscular SN-mesoporphyrin, a potent inhibitor of
heme oxygenase activity, in ameliorating jaundice in G6PD-deficient
newborns in Greece. When compared with an untreated control group and a
group of G6PD-normal newborns, a single dose of SN-mesoporphyrin shifted
the peak plasma bilirubin concentration distribution to lower values,
even in relation to normal neonates, and entirely eliminated the need
for phototherapy.

INHERITANCE

- X-chromosome Inactivation

Puck and Willard (1998) reviewed the mechanism for a skewed pattern of
X-chromosome inactivation in females heterozygous for X-linked traits.
Their Figure 1 diagrammed 3 different mechanisms for an extremely
unbalanced pattern of somatic cell mosaicism in women after X
inactivation. Luzzatto and Martini (1998) noted that at least one
possible example of each of the 3 mechanisms at work in different women
with G6PD deficiency can be pointed to. The first mechanism (the extreme
end of a normal distribution curve after random X inactivation) was
deemed the simplest explanation for the G6PD values in the fully
deficient range reported by Rinaldi et al. (1976) in about 1% of
genetically confirmed heterozygotes for the Mediterranean variant of
G6PD deficiency (305900.0006). The second mechanism could be called
'somatic selection after X inactivation.' Luzzatto and Martini (1998)
preferred this term to 'nonrandom X inactivation' because, in fact, X
inactivation itself is still random. This mechanism has been well
characterized (Filosa et al., 1996) in many heterozygous mothers of
patients with chronic nonspherocytic hemolytic anemia due to G6PD
deficiency. Here, the selection affects hematopoietic cells in a way
that is analogous to what happens to lymphoid cells in immunodeficiency
syndromes. As for the third mechanism, G6PD Ilesha (305900.0004) was
observed by Luzzatto et al. (1979) in a family in which every
heterozygous woman had an extremely unbalanced X-inactivation pattern,
which could not have resulted from selection against the cells with G6PD
Ilesha, because in some members of the family, the imbalance favored the
X chromosome with a normal G6PD allele, whereas in other members, it
favored the X chromosome with the G6PD Ilesha allele. Although at the
time of report the explanation favored was selection for cells
expressing a selectable allele of some other X-linked gene, there may
have been a defect in the X-inactivation process in this family. Since
the X-inactivation-specific transcript (XIST; 314670) gene maps to Xq13
and G6PD maps to Xq28, one would predict an even chance of
recombination, in keeping with what was observed in the family with the
G6PD Ilesha mutation.

POPULATION GENETICS

Miwa and Fujii (1996) stated that an estimated 400 million people
worldwide have G6PD deficiency associated with chronic hemolytic anemia
and/or drug- or infection-induced acute hemolytic attacks.

The highest prevalence of G6PD deficiency is found in Africa, southern
Europe, the Middle East. Southest Asia, and the central and southern
Pacific islands (summary by Cappellini and Fiorelli, 2008).

MOLECULAR GENETICS

Variants of G6PD deficiency have been divided into 5 classes according
to the level of enzyme activity: class 1--severe enzyme deficiency
associated with chronic nonspherocytic hemolytic anemia; class 2--severe
enzyme deficiency (less than 10%) associated with acute hemolytic
anemia; class 3--moderate to mild enzyme deficiency (10-60%); class
4--very mild or no enzyme deficiency (60%); class 5--increased enzyme
activity. Mutations causing nonspherocytic hemolytic anemia are
clustered near the carboxy end of the enzyme, in the region between
amino acids 362 and 446, whereas most of the clinically mild mutations
are located at the amino terminal end of the molecule. As the intragenic
defects have been identified, many variants that were thought to be
unique have been found to be identical on sequence analysis (Beutler et
al, 1991).

In patients with nonspherocytic hemolytic anemia, Beutler et al. (1992)
identified missense mutations in the G6PD gene (see, e.g., 305900.0035;
305900.0037-305900.0040).

Filosa et al. (1996) analyzed fractionated blood cells in 4
heterozygotes for the class 1 G6PD mutations G6PD Portici (305900.0008)
and G6PD Bari (1187G-T). In erythroid, myeloid, and lymphoid cell
lineages there was a significant excess of G6PD-normal cells, suggesting
that a selective mechanism operates at the level of pluripotent blood
stem cells. They concluded that their studies provided evidence that
severe G6PD deficiency adversely affects the proliferation or survival
of nucleated blood cells.

Vulliamy et al. (1998) determined the causative mutation in 12 cases of
G6PD deficiency associated with chronic nonspherocytic hemolytic anemia.
In 11 cases, the mutation they found had previously been reported in
unrelated individuals. These mutations comprised 7 different missense
mutations and a 24-bp deletion, G6PD Nara (305900.0052), previously
found in a Japanese boy. Repeated findings of the same mutations suggest
that a limited number of amino acid changes can produce the chronic
nonspherocytic hemolytic anemia phenotype and be compatible with normal
development. They found 1 new mutation, G6PD Serres (305900.0051).

GENOTYPE/PHENOTYPE CORRELATIONS

Miwa and Fujii (1996) listed the mutations responsible for about 78 G6PD
variants. Molecular studies disclosed that most of the class 1 G6PD
variants associated with chronic hemolysis have the mutations
surrounding either the substrate- or NADP-binding site.

Costa et al. (2000) pointed out that G6PD mutants causing class 1
variants (the most severe forms of the disease) cluster within exon 10,
in a region that, at the protein level, is believed to be involved in
dimerization. They identified a class 1 variant (G6PD Aveiro) mapping to
exon 8 (305900.0053).

HISTORY

Beaconsfield et al. (1965) advanced the hypothesis that the incidence of
cancer is inversely related to the frequency of G6PD deficiency in
blacks.

Since the metabolism of xylitol remains intact in G6PD-deficient red
cells, Wang et al. (1971) suggested use of xylitol in the treatment of
hemolytic crisis.

ANIMAL MODEL

Lee et al. (1981) observed G6PD heterozygosity in female hares. Pretsch
et al. (1988) recovered a mouse with X-linked G6PD deficiency from the
offspring of 1-ethyl-1-nitrosourea-treated male mice.

Stockham et al. (1994) observed G6PD deficiency causing persistent
hemolytic anemia and hyperbilirubinemia in a male American Saddlebred
horse. The dam had abnormalities consistent with heterozygosity.

Longo et al. (2002) crossed mouse chimeras from embryonic stem cells in
which the G6pd gene had been targeted with normal females.
First-generation G6pd heterozygotes born from this cross were
essentially normal; their tissues demonstrated strong selection for
cells with the targeted G6pd allele on the inactive X chromosome. When
these first-generation heterozygous females were bred to normal males,
only normal G6pd mice were born. There were 3 reasons for this:
hemizygous G6pd male embryos' development was arrested from embryonic
day 7.5, the time of onset of blood circulation, and they died by
embryonic day 10.5; heterozygous G6pd females showed abnormalities from
embryonic day 8.5, and died by embryonic day 11.5; and severe pathologic
changes were present in the placenta of both G6pd hemizygous and
heterozygous embryos. Thus, G6PD is not indispensable for early
embryonic development; however, severe G6PD deficiency in the
extraembryonic tissues (consequent on selective inactivation of the
normal paternal G6PD allele) impairs the development of the placenta and
causes death of the embryo. Most importantly, G6PD is indispensable for
survival when the embryo is exposed to oxygen through its blood supply.

*FIELD* RF
1. Beaconsfield, P.; Rainsbury, R.; Kalton, G.: Glucose-6-phosphate
dehydrogenase deficiency and the incidence of cancer. Oncologia 19:
11-19, 1965.

2. Beutler, E.: G6PD deficiency. Blood 84: 3613-3636, 1994.

3. Beutler, E.: The hemolytic effect of primaquine and related compounds:
a review. Blood 14: 103-139, 1959.

4. Beutler, E.; Kuhl, W.; Gelbart, T.; Forman, L.: DNA sequence abnormalities
of human glucose-6-phosphate dehydrogenase variants. J. Biol. Chem. 266:
4145-4150, 1991.

5. Beutler, E.; Westwood, B.; Prchal, J. T.; Vaca, G.; Bartsocas,
C. S.; Baronciani, L.: New glucose-6-phosphate dehydrogenase mutations
from various ethnic groups. Blood 80: 255-256, 1992.

6. Cappellini, M. D.; Fiorelli, G.: Glucose-6-phosphate dehydrogenase
deficiency. Lancet 371: 64-74, 2008.

7. Carson, P. E.; Flanagan, C. L.; Ickes, C. E.; Alving, A. S.: Enzymatic
deficiency in primaquine-sensitive erythrocytes. Science 124: 484-485,
1956.

8. Cocco, P.; Todde, P.; Fornera, S.; Manca, M. B.; Manca, P.; Sias,
A. R.: Mortality in a cohort of men expressing the glucose-6-phosphate
dehydrogenase deficiency. Blood 91: 706-709, 1998.

9. Cooper, M. R.; Dechatelet, L. R.; McCall, C. E.; Lavia, M. F.;
Spurr, C. L.; Baehner, R. L.: Complete deficiency of leukocyte glucose-6-phosphate
dehydrogenase with defective bactericidal activity. J. Clin. Invest. 51:
769-778, 1972.

10. Costa, E.; Cabeda, J. M.; Vieira, E.; Pinto, R.; Pereira, S. A.;
Ferraz, L.; Santos, R.; Barbot, J.: Glucose-6-phosphate dehydrogenase
Aveiro: a de novo mutation associated with chronic nonspherocytic
hemolytic anemia. Blood 95: 1499-1501, 2000.

11. Ferraris, A. M.; Broccia, G.; Meloni, T.; Forteleoni, G.; Gaetani,
G. F.: Glucose-6-phosphate dehydrogenase deficiency and incidence
of hematologic malignancy. Am. J. Hum. Genet. 42: 516-520, 1988.

12. Filosa, S.; Giacometti, N.; Wangwei, C.; De Mattia, D.; Pagnini,
D.; Alfinito, F.; Schettini, F.; Luzzatto, L.; Martini, G.: Somatic-cell
selection is a major determinant of the blood-cell phenotype in heterozygotes
for glucose-6-phosphate dehydrogenase mutations causing severe enzyme
deficiency. Am. J. Hum. Genet. 59: 887-895, 1996.

13. Gray, G. R.; Stamatoyannopoulos, G.; Naiman, S. C.; Kliman, M.
R.; Klebanoff, S. J.; Austin, T.; Yoshida, A.; Robinson, G. C. G.
: Neutrophil dysfunction, chronic granulomatous disease, and non-spherocytic
haemolytic anaemia caused by complete deficiency of glucose-6-phosphate
dehydrogenase. Lancet 302: 530-534, 1973. Note: Originally Volume
II.

14. Kappas, A.; Drummond, G. S.; Valaes, T.: A single dose of Sn-mesoporphyrin
prevents development of severe hyperbilirubinemia in glucose-6-phosphate
dehydrogenase-deficient newborns. Pediatrics 108: 25-30, 2001.

15. Lee, K. T.; Thomas, W. A.; Janakidevi, K.; Kroms, M.; Reiner,
J. M.; Borg, K. Y.: Mosaicism in female hybrid hares heterozygous
for glucose-6-phosphate dehydrogenase (G-6-PD). I. General properties
of a hybrid hare model with special reference to atherogenesis. Exp.
Molec. Path. 34: 191-201, 1981.

16. Longo, L.; Vanegas, O. C.; Patel, M.; Rosti, V.; Li, H.; Waka,
J.; Merghoub, T.; Pandolfi, P. P.; Notaro, R.; Manova, K.; Luzzatto,
L.: Maternally transmitted severe glucose 6-phosphate dehydrogenase
deficiency is an embryonic lethal. EMBO J. 21: 4229-4239, 2002.

17. Luzzatto, L.; Martini, G.: X-Linked Wiskott-Aldrich syndrome
in a girl. (Letter) New Eng. J. Med. 338: 1850-1851, 1998.

18. Luzzatto, L.; Usanga, E. A.; Bienzle, U.; Esan, G. F. J.; Fusuan,
F. A.: Imbalance in X-chromosome expression: evidence for a human
X-linked gene affecting growth of hemopoietic cells. Science 205:
1418-1420, 1979.

19. Mallouh, A. A.; Abu-Osba, Y. K.: Bacterial infections in children
with glucose-6-phosphate dehydrogenase deficiency. J. Pediat. 111:
850-852, 1987.

20. Meloni, T.; Carta, F.; Forteleoni, G.; Carta, A.; Ena, F.; Meloni,
G. F.: Glucose 6-phosphate dehydrogenase deficiency and cataract
of patients in northern Sardinia. Am. J. Ophthal. 110: 661-664,
1990.

21. Miwa, S.; Fujii, H.: Molecular basis of erythroenzymopathies
associated with hereditary hemolytic anemia: tabulation of mutant
enzymes. Am. J. Hemat. 51: 122-132, 1996.

22. Ninfali, P.; Baronciani, L.; Bardoni, A.; Bresolin, N.: Muscle
expression of glucose-6-phosphate dehydrogenase deficiency in different
variants. Clin. Genet. 48: 232-237, 1995.

23. Orzalesi, N.; Sorcinelli, R.; Guiso, G.: Increased incidence
of cataracts in male subjects deficient in glucose-6-phosphate dehydrogenase. Arch.
Ophthal. 99: 69-70, 1981.

24. Pretsch, W.; Charles, D. J.; Merkle, S.: X-linked glucose-6-phosphate-dehydrogenase
deficiency in Mus musculus. Biochem. Genet. 26: 89-103, 1988.

25. Puck, J. M.; Willard, H. F.: X inactivation in females with X-linked
disease. New Eng. J. Med. 338: 325-327, 1998.

26. Rinaldi, A.; Filippi, G.; Siniscalco, M.: Variability of red
cell phenotypes between and within individuals in an unbiased sample
of 77 heterozygotes for G6PD deficiency in Sardinia. Am. J. Hum.
Genet. 28: 496-505, 1976.

27. Ruwando, C.; Khea, S. C.; Snow, R. W.; Yates, S. N. R.; Kwiatkoweld,
D.; Gupta, S.; Warn, P.; Alisopp, G. E. M.; Gilbert, S. C.; Peschu,
N.; Newbold, C. I.; Greenwood, S. M.; Marsh, K.; Hill, A. V. S.:
Natural selection of hemi- and heterozygotes for G6PD deficiency in
Africa by resistance to severe malaria. Nature 376: 246-249, 1995.

28. Stockham, S. L.; Harvey, J. W.; Kinden, D. A.: Equine glucose-6-phosphate
dehydrogenase deficiency. Vet. Path. 31: 518-527, 1994.

29. Vulliamy, T. J.; Kaeda, J. S.; Ait-Chafa, D.; Mangerini, R.; Roper,
D.; Barbot, J.; Mehta, A. B.; Athanassiou-Metaxa, M.; Luzzatto, L.;
Mason, P. J.: Clinical and haematological consequences of recurrent
G6PD mutations and a single new mutation causing chronic nonspherocytic
haemolytic anaemia. Brit. J. Haemat. 101: 670-675, 1998.

30. Wang, Y. M.; Patterson, J. H.; Van Eys, J.: The potential use
of xylitol in glucose-6-phosphate dehydrogenase deficiency anemia. J.
Clin. Invest. 50: 1421-1428, 1971.

31. Zinkham, W. H.: A deficiency of glucose-6-phosphate dehydrogenase
activity in lens from individuals with primaquine-sensitive erythrocytes. Bull.
Johns Hopkins Hosp. 109: 206-216, 1961.

*FIELD* CD
Carol A. Bocchini: 10/23/2013

*FIELD* ED
carol: 10/28/2013
carol: 10/24/2013

MIM 305900
*RECORD*
*FIELD* NO
305900
*FIELD* TI
*305900 GLUCOSE-6-PHOSPHATE DEHYDROGENASE; G6PD
*FIELD* TX

DESCRIPTION

Glucose-6-phosphate dehydrogenase (G6PD; EC 1.1.1.49) plays a key role
read morein the production of ribose 5-phosphate and the generation of NADPH in
the hexose monophosphate pathway. Because this pathway is the only
NADPH-generation process in mature red cells, which lack the citric adid
cycle, a genetic deficiency of G6PD (300908) is often associated with
adverse physiologic effects (summary by Takizawa et al., 1986).

CLONING

Takizawa et al. (1986) cloned G6PD from a human hepatoma cDNA library.
The deduced 531-amino acid protein has a molecular mass of 58 kD.
Cappellini and Fiorelli (2008) stated that the G6PD protein contains 515
amino acids.

GENE STRUCTURE

Martini et al. (1986) determined that the human G6PD gene has 13 exons
and spans 18 kb. The protein-coding region is divided into 12 segments,
ranging from 12 to 236 bp, and an intron is present in the 5-prime
untranslated region. The major 5-prime end of mature G6PD mRNA in
several cell lines is located 177 bp upstream of the
translation-initiating codon. Comparison of the promoter region of G6PD
and 10 other housekeeping enzyme genes confirmed the presence of common
features. In particular, in 8 cases in which a 'TATA' box was present, a
conserved sequence of 25 bp was seen immediately downstream.

Chen et al. (1991) determined the sequence of 20,114 bp of human DNA
including the G6PD gene. The region included a prominent CpG island,
starting about 680 nucleotides upstream of the transcription initiation
site, extending about 1,050 nucleotides downstream of the initiation
site, and ending at the start of the first intron. The transcribed
region from the initiation site to the poly(A) addition site covered
15,860 bp. The sequence of the 13 exons agreed with the published cDNA
sequence and, for the 11 exons tested, with the corresponding sequence
in a yeast artificial chromosome (YAC). Sixteen Alu sequences
constituted 24% of the total sequence tract. Four were outside the
borders of the mRNA transcript of the gene; all of the others were found
in a large (9,858 bp) intron between exons 2 and 3.

The Japanese pufferfish Fugu rubripes is a useful model for the
comparative study of vertebrate genomes because of the compact nature of
its genome. Since the Fugu genome is approximately 8 times smaller than
that of mammals, most genes should be more compact. To test this
hypothesis, Mason et al. (1995) cloned and sequenced the G6PD gene from
Fugu and compared it to the corresponding human gene. The intron/exon
structure of the 2 genes was identical throughout the protein coding
regions. Intron 2 is also the largest intron in both species. However,
they found that the Fugu gene was 4 times smaller than the human gene;
the difference was accounted for by the fact that the pufferfish gene
has smaller introns. Mason et al. (1995) constructed a molecular
phylogeny for 10 G6PD protein sequences. The sequences fell in the
expected arrangement based on established phylogenetic relationships,
with the Plasmodium falciparum sequence diverging most widely.

Fusco et al. (2012) stated that the G6PD gene, which is transcribed in
the telomeric direction, partly overlaps the IKBKG gene (300248), which
is transcribed in the centromeric direction. The genes share a conserved
promoter region that has bidirectional housekeeping activity. In
addition, intron 2 of the G6PD gene contains an alternate promoter for
the IKBKG gene only. Fusco et al. (2012) determined that the region
containing the G6PD gene and the 5-prime end of the IKBKG gene contains
Alu elements.

EVOLUTION

Notaro et al. (2000) showed that an evolutionary analysis is a key to
understanding the biology of a housekeeping gene such as G6PD. From the
alignment of the amino acid sequence of 52 G6PD species from 42
different organisms, they found a striking correlation between the amino
acid replacements that cause G6PD deficiency in humans and the sequence
conservation of G6PD. Two-thirds of such replacements were found in
highly and moderately conserved (50 to 99%) amino acids; relatively few
were located in fully conserved amino acids (where they might be lethal)
or in poorly conserved amino acids (where presumably they simply would
not cause G6PD deficiency). The findings were considered consistent with
the notion that all human mutants have residual enzyme activity and that
null mutations are lethal at some stage of development. Comparing the
distribution of mutations in the human housekeeping gene with
evolutionary conservation is a useful tool for pinpointing amino acid
residues important for the stability or the function of the
corresponding protein.

MAPPING

Childs et al. (1958) determined that the G6PD gene resides on the X
chromosome.

From study of radiation-induced segregants (irradiated human cells
'rescued' by fusion with hamster cells), Goss and Harris (1977) showed
that the order of 4 loci on the X chromosome is PGK: alpha-GAL: HPRT:
G6PD and that the 3 intervals between these 4 loci are, in relative
terms, 0.33, 0.30, and 0.23.

Studying X-autosome translocations in somatic cell hybrids, Pai et al.
(1980) showed that a breakpoint at the junction of Xq27-q28 separates
HPRT from G6PD. G6PD is distally situated at Xq28. They localized HPRT
to the segment between Xq26 and Xq27.

That G6PD is X-linked in the mouse was supported by Epstein's finding
(1969) that oocytes of XO females have half as much G6PD as do oocytes
of XX female mice. The level of lactate dehydrogenase was the same.
Epstein's conclusion was that the G6PD gene is X-linked in the mouse,
that synthesis occurs in the oocyte and is dosage-dependent, and that X
inactivation does not occur in oocytes.

GENE FUNCTION

Ninfali et al. (1995) studied muscle expression of G6PD in normal
individuals and in persons with G6PD deficiency of 3 types. They were
prompted to undertake these studies because of patients with symptoms
such as myalgia, cramps, and muscle weakness under conditions of stress,
particularly physical exertion. All 3 variants--Mediterranean
(305900.0006), Seattle-like (305900.0010), and G6PD A-
(305900.0002)--showed the enzyme defect in muscle. A statistically
significant relationship was found in the activity of G6PD in
erythrocytes and muscle of male subjects. The results suggested to the
authors that, for a given variant, the extent of the enzyme defect in
muscle can be determined from the G6PD activity of erythrocytes, using
an equation that they derived.

In studies in bovine aortic and human coronary artery endothelial cells,
Leopold et al. (2007) demonstrated that aldosterone decreased G6PD
expression and activity, resulting in increased oxidant stress and
decreased nitric oxide levels, similar to what is observed in
G6PD-deficient endothelial cells. Aldosterone decreased G6PD expression
by increasing expression of the cAMP-response element modulator (CREM;
123812), thereby inhibiting cAMP-response element binding protein (CREB;
123810)-mediated G6PD transcription. In vivo aldosterone infusion in
mice decreased vascular G6PD expression and impaired vascular
reactivity; these effects were abrogated by spironolactone or vascular
gene transfer of G6pd. Leopold et al. (2007) concluded that aldosterone
induces a G6PD-deficient phenotype to impair endothelial function.

POPULATION GENETICS

Different variants of G6PD are found in high frequency in African,
Mediterranean, and Asiatic populations (Porter et al., 1964), and
heterozygote advantage vis-a-vis malaria (Luzzatto et al., 1969) has
been invoked to account for the high frequency of the particular alleles
in particular populations.

MOLECULAR GENETICS

The variety of forms of the G6PD enzyme is great (Yoshida et al., 1971;
Beutler and Yoshida, 1973; Yoshida and Beutler, 1978). The World Health
Organization (WHO, 1967,1967) gave its attention to problems of
nomenclature and standard procedures for study. The demonstrated
polymorphism at this X-linked locus rivals that of the autosomal loci
for the polypeptide chains of hemoglobin. As in the latter instance,
single amino acid substitution has been demonstrated as the basis of the
change in the G6PD molecule resulting from mutation (Yoshida et al.,
1967).

The G6PD variants have been divided into 5 classes according to the
level of enzyme activity: class 1--enzyme deficiency with chronic
nonspherocytic hemolytic anemia; class 2--severe enzyme deficiency (less
than 10%); class 3--moderate to mild enzyme deficiency (10-60%); class
4--very mild or no enzyme deficiency (60%); class 5--increased enzyme
activity. Mutations causing nonspherocytic hemolytic anemia are
clustered near the carboxy end of the enzyme, in the region between
amino acids 362 and 446, whereas most of the clinically mild mutations
are located at the amino end of the molecule. As the intragenic defects
have been identified, many variants that were thought to be unique have
been found to be identical on sequence analysis. This finding should not
be surprising inasmuch as the methods of biochemical characterization
are not very accurate, particularly when dealing with mutant enzymes
that are unstable. For example, although the patients were unrelated,
G6PD Marion, G6PD Gastonia, and G6PD Minnesota had the same
val213-to-leu substitution; and G6PD Nashville and G6PD Anaheim were
found to have the same arg393-to-his substitution (Beutler et al.,
1991).

The frequencies of low-activity alleles of G6PD in humans are highly
correlated with the prevalence of malaria (see 611162). These deficiency
alleles are thought to provide reduced risk for infection by the
Plasmodium parasite and are maintained at high frequency despite the
illnesses that they cause. Haplotype analysis of A- (305900.0002) and
Mediterranean (Med) (305900.0006) mutations at this locus indicates that
they had evolved independently and have increased in frequency at a rate
that is too rapid to be explained by random genetic drift. Tishkoff et
al. (2001) used statistical modeling to demonstrate that the A- allele
arose within a past 3840 to 11,760 years and the Med allele arose within
the past 1600 to 6640 years. Tishkoff et al. (2001) concluded that their
results support the hypothesis that malaria has had a major impact on
humans only since the introduction of agriculture within the past 10,000
years and provide a striking example of the signature of selection on
the human genome.

That resistance to severe malaria is the basis of the high frequency of
G6PD deficiency and that both hemizygotes and heterozygotes enjoy an
advantage was established by Ruwando et al. (1995) in 2 large
case-control studies of more than 2,000 African children. They found
that the common African form of G6PD deficiency (G6PD A-; 305900.0002)
was associated with a 46 to 58% reduction in risk of severe malaria for
both female heterozygotes and male hemizygotes. A mathematical model
incorporating the measured selective advantage against malaria suggested
that a counterbalancing selective disadvantage, associated with this
enzyme deficiency, has retarded its rise in frequency in malaria-endemic
regions.

Sansone et al. (1981) described 6 G6PD variants in Italian males, all
associated with enzyme deficiency and 2 with signs of hemolysis. They
provided a useful map of 19 sporadic G6PD variants found in Italy. They
mapped to regions where the common forms of G6PD deficiency are
frequent.

Hitzeroth and Bender (1981) found an increasing frequency of apparent BB
homozygotes with increasing age of groups of South African blacks
studied. They suggested that this represents selection against A- cell
lines in heterozygotes and speculated further that malaria is the
underlying selective agent.

Mohrenweiser and Neel (1981) identified thermolabile variants of lactate
dehydrogenase B, glucosephosphate isomerase, and glucose-6-phosphate
dehydrogenase. None was detectable as a variant by standard
electrophoretic techniques. All were inherited. Beutler (1983)
hypothesized that the marked differences in the extent to which various
tissues manifest the deficiency state in various enzymopathies including
G6PD deficiency may be related to tissue-to-tissue differences in
proteases. Mutation may produce changes in susceptibility of the enzyme
to proteases.

Data on gene frequencies of allelic variants were tabulated by
Roychoudhury and Nei (1988).

Vulliamy et al. (1988) cloned and sequenced 7 mutant G6PD alleles. A
single point mutation in the African variant G6PD A (305900.0001) does
not result in deficiency of the enzyme. The other 6 mutants were all
associated with enzyme deficiency. Single point mutations were
identified in G6PD Mediterranean (305900.0006), G6PD Metaponto
(305900.0007), G6PD Ilesha (305900.0004), G6PD Chatham (305900.0003),
G6PD Santiago de Cuba (305900.0009), and G6PD Matera (an example of A-;
305900.0002).

By use of 14 unique sequence probes and 18 restriction enzymes, D'Urso
et al. (1988) found a polymorphic silent mutation in the G6PD gene. A
PstI site that maps to exon 10 was monomorphic in all British and
Italian subjects studied, but was polymorphic in West African people.
Specifically, it was absent from 22% of Nigerian X chromosomes. By
sequence analysis, D'Urso et al. (1988) showed that the absence of this
PstI site resulted from a G-to-A replacement at position 1116,
corresponding to the third base of a glutamine codon (see 305900.0017).
No amino acid change was produced in the protein. Yoshida et al. (1988)
reported 2 RFLPs of the G6PD locus with high frequency in blacks and
showed statistically significant linkage disequilibrium between the
A+/B+ types and 1 of the RFLPs at the G6PD locus.

Vulliamy et al. (1988) found a striking predominance of C-to-T
transitions among the G6PD mutations, with GC doublets involved in 4 of
the 7 cases. It has been found that even in the same population, more
than 1 G6PD variant is present. For example, in the island of Sardinia,
extensive clinical and biochemical studies identified 4 different G6PD
variants. De Vita et al. (1989) cloned and sequenced the 4 G6PD variants
and found that at the molecular level there were only 2 mutations. The
first mutation had an asp282-to-his change resulting from a GAT-to-CAT
change in exon 8. This mutation caused the G6PD Seattle-like phenotype,
a relatively mild form of G6PD deficiency (see 305900.0010). The other 3
variants were accompanied by very severe G6PD deficiency. All 3 had a
ser188-to-phe change resulting from a TCC-to-TTC transition. This is the
same change as that in G6PD Mediterranean (305900.0006). These 3
Sardinian variants also had a silent mutation in exon 11 with a change
of TAC-to-TAT, both of which encode tyrosine at amino acid 437. These
findings indicate that some G6PD-deficient variants identified only on
the basis of their biochemical characteristics may not correspond to
different mutations in the G6PD gene. The variations may be due to
posttranscriptional or posttranslational modifications of the enzyme;
whether the modifications are due to mutations in a tightly linked gene
or to noninherited physiologic changes could not be distinguished with
the data available. Study of families in which different forms of G6PD
Mediterranean segregate suggested that the biochemical characteristics
are transmitted in the family along with the enzyme deficiency, thus
favoring the first hypothesis.

In a study of an unselected sample of 1,524 schoolboys from the province
of Matera (Lucania) in southern Italy, Calabro et al. (1990) found that
although the most frequent form of G6PD deficiency was G6PD
Mediterranean, an extraordinary number of other forms existed. The
overall rate of G6PD deficiency was 2.6%. The frequency ranged from 7.2%
on the Ionian coast to zero on the eastern side of the Lucanian
Apennines.

Kay et al. (1992) analyzed the evolution of the G6PD gene by examining
the DNA samples from 54 male African Americans for G6PD A+
(305900.0001), G6PD A- (305900.0002), and G6PD B and for polymorphisms
in intron 5 (PvuII), at nucleotide 1311 (305900.0018), and at nucleotide
1116 (305900.0017). They concluded from these and their previous studies
that G6PD B is the most ancient genotype. The nucleotide 1311 mutation,
with its worldwide distribution, probably occurred next. The PstI
mutation, limited to Africans, probably arose next and is more ancient
than the A+ mutation, which occurred in a gene without either the PstI
or the 1311 mutation. G6PD A- (202A/376G) is the most recent mutation
and is still in linkage disequilibrium with all of the sites. It
presumably occurred in an individual with both the A+ and PvuII
mutations.

Chiu et al. (1993) reported molecular characterization of the defects in
43 G6PD-deficient Chinese males whose G6PD had been well characterized
biochemically. Among the 43 samples, they identified 5 different
nucleotide substitutions: 1388G-A (arg to his; 305900.0029); 1376G-T
(arg to leu; 305900.0021); 1024C-T (leu to phe; 305900.0046); 392G-T
(gly to val; 305900.0045); and 95A-G (his to arg; 305900.0044). The 5
substitutions accounted for 36 of the 43 samples; none of these
substitutions had been reported in non-Asians. The substitutions at
nucleotides 392 and 1024 were new findings. The substitutions at
nucleotides 1376 and 1388 accounted for over one-half of the samples.

Vulliamy et al. (1993) tabulated 58 different mutations in the G6PD gene
that account for 97 named G6PD variants. The mutations were almost
exclusively missense mutations, causing single amino acid substitutions.
They were spread throughout the coding region of the gene, although
there appeared to be a clustering of mutations that caused a more severe
clinical phenotype towards the 3-prime end of the gene. The absence of
large deletions, frameshift mutations, and nonsense mutations was
considered consistent with the notion that a total lack of G6PD activity
would be lethal.

Miwa and Fujii (1996) listed the mutations responsible for about 78 G6PD
variants.

Mason (1996) reviewed information on the G6PD enzyme and on mutations in
the gene. A map of 515 amino acids showing the location of mutations,
including double mutations, was provided.

Filosa et al. (1996) analyzed fractionated blood cells in 4
heterozygotes for the class 1 G6PD mutations G6PD Portici (305900.0008)
and G6PD Bari (1187G-T). In erythroid, myeloid, and lymphoid cell
lineages there was a significant excess of G6PD-normal cells, suggesting
that a selective mechanism operates at the level of pluripotent blood
stem cells. They concluded that their studies provided evidence that
severe G6PD deficiency adversely affects the proliferation or survival
of nucleated blood cells.

Liu et al. (1997) reported a method of determination of clonality using
allele-specific PCR (ASPCR) to detect exonic polymorphisms in p55
(305360) and G6PD. They demonstrated a significant sex difference in
allele frequencies in African Americans but not in Caucasians, and
linkage disequilibrium for the p55 and G6PD alleles in Caucasians but
not in African Americans.

Vulliamy et al. (1998) determined the causative mutation in 12 cases of
G6PD deficiency associated with chronic nonspherocytic hemolytic anemia.
In 11 cases, the mutation they found had previously been reported in
unrelated individuals. These mutations comprised 7 different missense
mutations and a 24-bp deletion, G6PD Nara (305900.0052), previously
found in a Japanese boy. Repeated findings of the same mutations suggest
that a limited number of amino acid changes can produce the chronic
nonspherocytic hemolytic anemia phenotype and be compatible with normal
development. They found 1 new mutation, G6PD Serres (305900.0051).

Cappadoro et al. (1998) presented evidence suggesting that early
phagocytosis of G6PD-deficient erythrocytes parasitized by Plasmodium
falciparum may explain malaria protection in G6PD deficiency.

Kwok et al. (2002) described a Web-accessible database of G6PD
mutations. The relational database integrates up-to-date mutational and
structural data from various databanks with biochemically characterized
variants and their associated phenotypes obtained from published
literature and a Favism website.

Barisic et al. (2005) identified 5 different mutations in the G6PD gene
in 24 unrelated males with G6PD deficiency from the Dalmatian region of
southern Croatia. The variants included Cosenza (305900.0059) (37.5% of
patients), Mediterranean (305900.0006) (16.6%), Seattle (12.5%), Union
(12.5%), Cassano (4.2%), and a novel variant, termed G6PD Split
(305900.0059) (4.2%). The variants in 3 patients (12.5%) were
uncharacterized.

Ninokata et al. (2006) identified G6PD deficiency in 9.8% of males and
10.4% of females among 345 healthy adults on Phuket island in southern
Thailand. Although none of the individuals had molecular evidence of
malaria infection, the findings suggested that malaria endemics had
occurred in the past and that G6PD deficiency has been maintained as an
advantageous genetic trait in this population. At least 5 different G6PD
variants were identified, suggesting that several Asian ethnic groups,
such as Burmese, Laotian, Cambodian, Thai, and Chinese, participated in
establishing the current ethnic identity of the population of Phuket.

Jiang et al. (2006) identified 14 different mutations in the G6PD gene
among 1,004 G6PD-deficient Chinese individuals comprising 11 ethnic
groups. The variants varied in frequency across the ethnic groups and
correlated geographically with historical patterns of malaria. The
variants were different from those reported in African, European, and
Indian populations. The most common variants in the Chinese population
were G6PD Kaiping (R463H; 305900.0029) and G6PD Canton (R459L;
305900.0021), accounting for over 60% of G6PD-deficient individuals, and
Gaohe (H32R; 305900.0044). In vitro functional expression studies in E.
coli showed significantly decreased enzyme activity for all 3 mutant
proteins. All 3 variants showed decreased Km for G6P, but whereas the
Canton and Kaiping variants had increased Km for NADP+, the Gaohe
variant showed decreased Km for NADP+, likely reflecting compensation in
the latter variant. Jiang et al. (2006) concluded that residues arg459
and arg463 play an important role in anchoring NADP+ to the catalytic
domain of the enzyme.

GENOTYPE/PHENOTYPE CORRELATIONS

Miwa and Fujii (1996) stated that most of the class 1 G6PD variants
associated with chronic hemolysis have the mutations surrounding either
the substrate- or NADP-binding site.

Costa et al. (2000) pointed out that G6PD mutants causing class 1
variants (the most severe forms of the disease) cluster within exon 10,
in a region that, at the protein level, is believed to be involved in
dimerization. They identified a class 1 variant mapping to exon 8
(305900.0053).

ANIMAL MODEL

Longo et al. (2002) crossed mouse chimeras from embryonic stem cells in
which the G6pd gene had been targeted with normal females.
First-generation G6pd heterozygotes born from this cross were
essentially normal; their tissues demonstrated strong selection for
cells with the targeted G6pd allele on the inactive X chromosome. When
these first-generation heterozygous females were bred to normal males,
only normal G6pd mice were born. There were 3 reasons for this:
hemizygous G6pd male embryos' development was arrested from embryonic
day 7.5, the time of onset of blood circulation, and they died by
embryonic day 10.5; heterozygous G6pd females showed abnormalities from
embryonic day 8.5, and died by embryonic day 11.5; and severe pathologic
changes were present in the placenta of both G6pd hemizygous and
heterozygous embryos. Thus, G6PD is not indispensable for early
embryonic development; however, severe G6PD deficiency in the
extraembryonic tissues (consequent on selective inactivation of the
normal paternal G6PD allele) impairs the development of the placenta and
causes death of the embryo. Most importantly, G6PD is indispensable for
survival when the embryo is exposed to oxygen through its blood supply.

In ischemia-reperfusion experiments on isolated mouse hearts, Jain et
al. (2004) demonstrated that G6pd is rapidly activated without a change
in G6pd protein levels. G6pd -/- hearts had greatly impaired cardiac
relaxation and contractile performance, associated with depletion of
total glutathione stores and impaired generation of reduced glutathione,
compared to wildtype hearts. Increased ischemia-reperfusion injury was
reversed by antioxidant treatment but unaffected by supplementation of
ribose stores. Jain et al. (2004) concluded that G6PD is an essential
myocardial antioxidant enzyme, required for maintaining cellular
glutathione levels and protecting against oxidative stress-induced
cardiac dysfunction during ischemia-reperfusion.

HISTORY

Polymorphism at the G6PD locus has made it a useful X-chromosome marker,
like the colorblindness and Xg blood group loci; close linkage of the
colorblindness loci, the G6PD locus, and the hemophilia A locus (Adam et
al., 1967; Boyer and Graham, 1965) has been demonstrated. Also, as a
biochemical phenotype identifiable at the cellular level, G6PD variants
have been useful in somatic cell genetics, permitting, for example, one
of the critical proofs in man of the Lyon hypothesis (Davidson et al.,
1963).

The relative stability of the X chromosome during evolution has been
shown by the fact that the G6PD locus is X-borne also in a number of
other species (Ohno, 1967). G6PD and HPRT are linked in the Chinese
hamster (Rosenstraus and Chasin, 1975) and presumably are on the X
chromosome as in man. By study of cell hybrids, Shows et al. (1976)
found that HPRT and G6PD are closely linked in the Muntjac deer. Smith
et al. (1976) found G6PD deficiency in a male Weimaraner dog, but were
not able to do genetic studies. Alpha-GAL, HPRT, PGK and G6PD are
X-linked in the rabbit, according to mouse-rabbit hybrid cell studies
(Cianfriglia et al., 1979; Echard and Gillois, 1979). By comparable
methods, Hors-Cayla et al. (1979) found them to be X-linked also in
cattle. According to cell hybridization studies, HPRT, G6PD, and PGK are
X-linked in the pig (Gellin et al., 1979) and in sheep (Saidi et al.,
1979). Using pulsed field gel electrophoresis, Faust et al. (1992)
demonstrated that, in the mouse, Gdx (312070), P3 (312090), and G6pd are
physically linked to the X-linked visual pigment locus (Rsvp) within a
maximal distance of 340 kb, while G6pd and f8 (300841) are approximately
900 kb apart.

G6PD Hektoen is characterized by increased red cell enzyme activity. It
is, therefore, a class 5 G6PD variant. It was first described by Dern et
al. (1969). Yoshida (1970) thought that the variant peptide had
replacement of histidine by tyrosine. Later, Yoshida (1996) was
uncertain about this conclusion and stated that the basic defect remains
to be identified.

*FIELD* AV
.0001
G6PD A+
G6PD, ASN126ASP

See Kirkman et al. (1964) and Yoshida et al. (1967). Takizawa and
Yoshida (1987) found that the G6PD A+ gene has an A-to-G transition,
resulting in the substitution of aspartic acid for asparagine as the
142nd amino acid from the N-terminus of the enzyme. Hirono and Beutler
(1988) showed that a mutation responsible for the G6PD A- phenotype
present in enzyme-deficient (300908) West African and American blacks
occurred in a gene that produces the G6PD A+ phenotype. A substitution
of guanine for adenine at nucleotide 376 (in exon 5) was found in all
G6PD A+ and G6PD A- samples but in none of the G6PD B+ samples examined.
Substitution of adenine for guanine at nucleotide 202 was found in 4 of
5 G6PD A- samples; this change is apparently responsible for the in vivo
instability of the enzyme protein. Thus, the difference distinguishing
the A and B forms of G6PD is the amino acid at residue 126 (see
305900.0002). Presumably as the result of alternative splicing, there is
considerable heterogeneity among different G6PD cDNAs.

Both the variant A (with enzyme activity in the normal range, also
called A) and the variant A- (associated with enzyme deficiency) have a
frequency of about 0.2 in several African populations. Two restriction
fragment length polymorphisms have also been found in people of African
descent but not in other populations, whereas a silent mutation has been
shown to be polymorphic in Mediterranean, Middle Eastern, African, and
Indian populations. Vulliamy et al. (1991) reported 2 additional
polymorphisms detected by sequence analysis, one in intron 7 and one in
intron 8. Analysis of 54 African males for the 7 polymorphic sites
clustered within 3 kb of the G6PD gene showed only 7 of the 128 possible
haplotypes, thus indicating marked linkage disequilibrium. These data
enabled Vulliamy et al. (1991) to suggest an evolutionary pathway for
the different mutations, with only a single ambiguity. The mutation
underlying the A variant is the most ancient and the mutation underlying
the A- variant is the most recent. Since it seemed reasonable that the
A- allele is subject to positive selection by malaria, whereas the other
alleles are neutral, Vulliamy et al. (1991) suggested that G6PD may lend
itself to the analysis of the role of random genetic drift and selection
in determining allele frequencies within a single genetic locus in human
populations.

.0002
G6PD A-
G6PD MATERA;;
G6PD BETICA;;
G6PD CASTILLA;;
G6PD DISTRITO FEDERAL;;
G6PD TEPIC
G6PD, VAL68MET, ASN126ASP

Babalola et al. (1976) predicted that the A- mutation may have occurred
in an individual carrying the A+ mutation. A black individual with the
G6PD A- phenotype but no mutation at nucleotide 202 suggested that this
individual may have another mutation that caused instability and thus
deficiency of the enzyme. Yoshida and Takizawa (1988) presented evidence
that the A- gene evolved by stepwise mutations through the A+ gene.

Vulliamy et al. (1988) cloned and sequenced 7 mutant G6PD alleles. A
single point mutation in the African variant G6PD A does not result in
deficiency of the enzyme. The other 6 mutants, including G6PD A-, were
all associated with enzyme deficiency. Two different point mutations
were found in G6PD A-, 1 of which was the same as that in G6PD A. See
Yoshida et al. (1967). Hirono and Beutler (1988) demonstrated a
substitution of methionine for valine at position 68 resulting from a
G-to-A change at nucleotide 202 (in exon 4). The in vivo instability of
the enzyme is the result of this change. The gene also has the change at
amino acid 126 characteristic of G6PD A. See Vulliamy et al. (1988).

Beutler and Kuhl (1990) performed haplotyping with 4 polymorphic
restriction sites in the G6PD locus in DNA samples from 29 males with
the G6PD A- phenotype and 14 males with a G6PD B phenotype. All G6PD A-
subjects with the G6PD A- (202A/376G) genotype, regardless of population
origin, shared identical haplotypes. One of the restriction sites is
uncommon in the populations studied; thus, Beutler and Kuhl (1990)
considered it likely that the G6PD A- mutation at nucleotide 202 arose
relatively recently and in a single person. The 5 populations screened
were black (16), Puerto Rican (2), Mexican (4), white US (1), and
Spanish (3). One G6PD A- male was of the 376G/680T genotype and 2 were
of the 376G/968C genotype.

Calabro et al. (1990) found this mutation, regarded as
characteristically African, in an unselected sample of 1,524 schoolboys
of the province of Matera in Southern Italy.

Beutler et al. (1991) found that 3 previously reported
electrophoretically fast Mexican G6PD variants--G6PD Distrito Federal
(Lisker et al., 1981), G6PD Tepic (Lisker et al., 1985), and G6PD
Castilla (Lisker et al., 1977)--all showed the changes characteristic of
G6PD A- (202A/376G) and had the haplotype characteristic of G6PD A- in
Africa. G6PD Betica (330:Vives-Corrons and Pujades, 1982; Vives-Corrons
et al., 1980), which is frequent in Spain, also had the same
characteristics. Since the PvuII+ genotype is rare in Europe, the G6PD
Betica mutation was presumably imported from Africa.

Hirono and Beutler (1988) found 2 other mutations that produced the G6PD
A- phenotype: arg227-to-leu and leu323-to-pro. In both cases the
mutations existed on the G6PD A background, i.e., the asn126-to-asp
substitution.

Town et al. (1992) demonstrated that both the val68-to-met and the
asn126-to-asp mutations found in G6PD A- are necessary to produce the
G6PD-deficient phenotype (rather than the val68-to-met mutation having
happened to arise in an A+ gene in the first instance). They approached
the question by introducing G6PD B, A, A-, and G6PD val68-to-met in a
bacterial expression system and analyzing their biochemical properties.
With each of the 2 mutations alone, they found a slight decrease in both
the specific activity and the yield of enzyme protein when compared to
G6PD B. When both mutations were introduced together, there was a
roughly additive effect on specific activity, but a much more drastic
effect on enzyme yield which was reduced to 4% of normal. They inferred
that the coexistence of the 2 mutations acted synergistically in causing
instability of the enzyme. This would explain why a B- phenotype has
only very rarely been observed. (Comparable results were produced when
the replacement gln119-to-glu was combined with val68 to met.)

G6PD A- is the most common polymorphic variant associated with
deficiency of G6PD in African populations, accounting for 20 to 40% of
the affected population in western and central Africa; the most common
nondeficient polymorphic variant in Africa is G6PD A. The G6PD A-
mutation at position 68 alone has not been detected in any variant;
this, together with further haplotyping analyses, led Vulliamy et al.
(1992) to suggest that the nondeficient single mutant G6PD A is more
ancient than the deficient double mutant G6PD A-.

Gomez-Gallego et al. (2000) performed structural studies on the doubly
mutant G6PD A-. The changes they observed did not affect the active site
of the mutant protein, since its spatial position was unmodified. The
result of the structural changes was a loss of folding determinants,
leading to a protein with decreased intracellular stability.
Gomez-Gallego et al. (2000) suggested that the resultant protein was the
cause of the enzyme deficiency in the red blood cell, which is unable to
perform de novo protein synthesis.

.0003
G6PD CHATHAM
G6PD, ALA335THR

Substitution of adenine for guanine at nucleotide 1003 leads to
substitution of alanine by threonine at amino acid position 335
(Vulliamy et al., 1988). This mutation has been found in 2 unrelated
Asian Indians and in a man from Syria and may be polymorphic. It causes
class 2 enzyme derangement. No change in restriction sites has been
found.

Mesbah-Namin et al. (2002) reported the first investigation of G6PD
deficiency (300908) among the Mazandaranians of northern Iran. They
analyzed the G6PD gene in 74 unrelated G6PD-deficient males with a
history of favism. Molecular analysis revealed 3 different major
polymorphic variants: G6PD Mediterranean (305900.0006) was found in 49
(66.2%), G6PD Chatham in 20 (27%), and G6PD Cosenza in 5 (6.75%) of the
patients. The prevalence of G6PD Chatham in this Iranian population was
the highest in the world. The distribution of the G6PD variants was more
similar to that found in an Italian population than in other Middle
Eastern countries.

.0004
G6PD ILESHA
G6PD, GLU156LYS

See Usanga et al. (1977) and Luzzatto et al. (1979). Substitution of
adenine for guanine at base 466 (in exon 5) leads to replacement of
glutamic acid by lysine (Vulliamy et al., 1988). This sporadic class 3
mutation is associated with loss of a HinfI site.

.0005
G6PD MAHIDOL
G6PD, GLY163SER

See Panich et al. (1972). A G-to-A change at base 487 (exon 6) leads to
substitution of serine for glycine at amino acid 163 (Vulliamy, 1989).
This mutation is polymorphic in Southeast Asia, causes class 2 enzyme
derangement, and is associated with a new AluI site (Vulliamy et al.,
1989). The same mutation was identified by Tang et al. (1992) in a
Taiwanese in Taiwan.

Matsuoka et al. (2004) found that 11% of blood samples from persons in
remote areas of Myanmar (former Burma) indicated G6PD deficiency. Taken
together with data from a previous report (Iwai et al., 2001), these
findings indicated that 91.3% of G6PD variants were G6PD Mahidol. The
findings suggested that the Myanmar population is derived from
homogeneous ancestries different from those of Thai, Malaysian, and
Indonesian populations.

Louicharoen et al. (2009) investigated the effect of the G6PD-Mahidol
487A variant on human survival related to P. vivax and P. falciparum
malaria in Southeast Asia. They showed that strong and recent positive
selection has targeted the Mahidol variant over the past 1,500 years.
The authors found that the G6PD-Mahidol variant reduces vivax, but not
falciparum, parasite density in humans, which indicates that P. vivax
has been a driving force behind the strong selective advantage conferred
by this mutation.

.0006
G6PD MEDITERRANEAN
G6PD SASSARI;;
G6PD CAGLIARI
G6PD, SER188PHE

See Kirkman et al. (1964), Ben-Bassat and Ben-Ishay (1969), Lenzerini et
al. (1969), Testa et al. (1980), and Morelli et al. (1984). A change
from cytosine to thymine at base position 563 (in exon 6) causes a
change from serine to phenylalanine in amino acid position 188 (Vulliamy
et al., 1988). De Vita et al. (1989) found that G6PD Mediterranean, G6PD
Sassari, and G6PD Cagliari have the same mutational change, resulting
from a TCC-to-TTC mutation in exon 6. There is a second silent mutation
of TAC-to-TAT at codon 437 in exon 11 (C-to-T at nucleotide 1311; see
305900.0018); both codons code for tyrosine. This mutation is a
polymorphism, causes class 2 abnormality, and creates a new MboII site.

Beutler and Kuhl (1990) studied the distribution of the nucleotide
polymorphism C1311T in diverse populations. Only 1 of 22 male subjects
from Mediterranean countries who had the G6PD Mediterranean-563T
genotype had a C at nucleotide 1311, which is the more frequent finding
in this group. In contrast, both G6PD Mediterranean-563T males from the
Indian subcontinent had the usual C at nucleotide 1311. Beutler and Kuhl
(1990) interpreted these findings as suggesting that the same mutation
at nucleotide 563 arose independently in Europe and in Asia.

Similar studies were done by Kurdi-Haidar et al. (1990) in 21 unrelated
individuals with G6PD Mediterranean from Saudi Arabia, Iraq, Iran,
Jordan, Lebanon, and Israel. All but 1 had the 563 mutation, and, of
these, all but 1 had the C-to-T change at nucleotide 1311. Among another
24 unrelated Middle Eastern persons with normal G6PD activity, 4 had the
silent mutation at position 1311 in the absence of the deficiency
mutation at position 563. Kurdi-Haidar et al. (1990) concluded that most
Middle Eastern subjects with the G6PD Mediterranean phenotype have the
same mutation as that found in Italy; that the silent mutation is an
independent polymorphism in the Middle East, with a frequency of about
0.13; and that the mutation leading to G6PD Mediterranean deficiency
probably arose on a chromosome that already carried the silent mutation.

In Nepal, Matsuoka et al. (2003) tested 300 males for G6PD deficiency
and identified 2 (0.67%) who were G6PD deficient. Compared with normal
controls, G6PD activity was 12% and 26%, respectively. Both subjects had
the 563C-T substitution of G6PD Mediterranean (ser188 to phe), and both
had the silent 1311C-T change. A similar second change has been
described in persons living in Mediterranean countries and Middle East
countries. However, the form of G6PD Mediterranean found in India and
Pakistan has no replacement at nucleotide 1311. Thus, the 2 subjects in
Kathmandu, Nepal, would be closer to people in Middle East countries
than people in India.

Corcoran et al. (1992) described a G6PD mutant biochemically
indistinguishable from the common variety due to a C-to-T mutation at
nucleotide 563. Instead, a C-to-T transition was found at nucleotide 592
in exon 6, changing an arginine residue to a cysteine residue only 10
amino acids downstream from the Mediterranean mutation. The new variant
was named G6PD Coimbra (305900.0031).

Kaplan et al. (1997) presented data suggesting that the coexistence of
Mediterranean type G6PD deficiency with the AT insertion polymorphism of
the promoter of the UGT1A1 gene (191740.0011), which is associated with
Gilbert syndrome (143500) in adults, is responsible for the development
of neonatal hyperbilirubinemia. This is the most devastating clinical
consequence of G6PD deficiency; it can be severe and result in
kernicterus or even death. Kaplan et al. (1997) found that neither G6PD
deficiency nor the polymorphism of UDP glucuronosyltransferase alone
increased the incidence of neonatal hyperbilirubinemia, but in
combination they did. The authors suggested that this gene interaction
may serve as a paradigm of the interaction of benign genetic
polymorphisms in the causation of disease.

Kaplan et al. (2001) reported 2 premature female neonates heterozygous
for the G6PD Mediterranean mutation who presented with severe
hyperbilirubinemia requiring exchange transfusions. Both had had normal
G6PD biochemical screening tests.

.0007
G6PD METAPONTO
G6PD, ASP58ASN

Substitution of adenine for guanine at base 172 (exon IV) leads to a
substitution of asparagine for aspartic acid at amino acid 58 (Vulliamy
et al., 1988). The mutation was found in a sporadic, class 3 case, and
no restriction site change was identified. See Calabro et al. (1990).

.0008
G6PD PORTICI
ANEMIA, NONSPHEROCYTIC HEMOLYTIC, DUE TO G6PD DEFICIENCY
G6PD, ARG393HIS

G6PD Portici has a G-to-A change at nucleotide 1178 of the G6PD gene,
resulting in substitution of histidine for arginine at residue 393
(Filosa, 1989). The mutation was found in a sporadic case of class 1
deficiency (300908) and is not associated with an identified restriction
site. In the full report, Filosa et al. (1992) described the kinetic
characteristics of this G6PD variant (Portici) which was associated with
chronic nonspherocytic hemolytic anemia.

.0009
G6PD SANTIAGO DE CUBA
ANEMIA, NONSPHEROCYTIC HEMOLYTIC, DUE TO G6PD DEFICIENCY
G6PD, GLY447ARG

Substitution of adenine for guanine as base number 1339 (exon 11) leads
to substitution of arginine for glycine at amino acid position 447
(Vulliamy et al., 1988). This variant is associated with severe chronic
hemolytic anemia (class 1; 300908). It was found in a sporadic case. A
new PstI site was created, and this was used to show that it was a new
mutation.

.0010
G6PD SEATTLE-LIKE
G6PD MODENA
G6PD, ASP282HIS

See Lenzerini et al. (1969) and Rattazzi et al. (1969). De Vita et al.
(1989) found that G6PD Seattle-like, which produces a relatively mild
phenotype, has substitution of histidine for aspartic acid at amino acid
282, resulting from a GAT-to-CAT change in exon 8. Cappellini et al.
(1994) found the same variant in an Italian man from the Po delta and
designated it G6PD Modena before finding that it had the same mutation
as that in G6PD Seattle-like. They stated that the G-to-C transition was
at nucleotide 844 in exon 8.

.0011
G6PD HARILAOU
G6PD, PHE216LEU

Town et al. (1990) described G6PD Harilaou in a Greek boy with severe
hemolytic anemia. Poggi (1989) found a T-to-G change at nucleotide 648
that leads to substitution of leucine for phenylalanine at residue 216.

.0012
G6PD IOWA
G6PD IOWA CITY;;
G6PD SPRINGFIELD;;
G6PD WALTER REED
G6PD, LYS386GLU

See Beutler et al. (1986). Hirono et al. (1989) demonstrated an A-to-G
substitution at nucleotide 1156, resulting in substitution of glutamic
acid for lysine at amino acid 386. This variant G6PD, as well as G6PD
Beverly Hills, Tomah, Riverside, and some others, is unstable in the
presence of 10 microM NADP+ (where normal G6PD is stable) but is
reactivated by 200 microM NADP+. G6PD Tomah, Iowa and Beverly Hills have
amino acid substitutions at positions 385, 386, and 387, respectively;
G6PD Riverside, with a substitution at position 410, shows weak
reactivation by NADP+. These observations, together with the fact that
these amino acids are highly conserved, led Hirono et al. (1989) to
propose that they are in the region of the molecule involved in NADP+
binding.

.0013
G6PD BEVERLY HILLS
G6PD, ARG387HIS

Hirono et al. (1989) demonstrated a G-to-A mutation at nucleotide 1160,
causing substitution of histidine for arginine-387. The mutation
destroyed an HhaI site.

.0014
G6PD TOMAH
G6PD, CYS385ARG

Hirono et al. (1989) demonstrated a T-to-C transition at nucleotide
1153, causing substitution of arginine for cysteine-385. The mutation
created an Fnu4HI restriction site, which was used to confirm the
mutation.

.0015
G6PD RIVERSIDE
G6PD, GLY410CYS

Hirono et al. (1989) demonstrated a G-to-T mutation at nucleotide 1228
that caused a change of glycine to cysteine at amino acid 410. The fact
that the mutation destroyed an NciI restriction site was used to confirm
the mutation.

.0016
G6PD MONTALBANO
G6PD, ARG285HIS

Viglietto et al. (1990) found a new variant with nearly normal
properties, due to a G-to-A transition that caused an
arginine-to-histidine substitution at position 285. See Calabro et al.
(1990).

.0017
G6PD RFLP
G6PD, NT1116, G-A

D'Urso et al. (1988) found a silent G-to-A change at nucleotide 1116 (in
exon 10), generating a PstI site.

.0018
G6PD RFLP
G6PD, NT1311, C-T

De Vita et al. (1989) found a silent C-to-T change at nucleotide 1311
(in exon 11).

.0019
G6PD RFLP
G6PD, EX6, -60, C-G

Yoshida et al. (1988) found a RFLP resulting from a substitution in
intron 5, creating a PvuII site. The probable change was C to G at a
position 60 nucleotides upstream from exon 6 (Luzzatto, 1990).

.0020
G6PD ANDALUS
G6PD, ARG454HIS

Vives-Corrons et al. (1990) studied a G6PD variant resembling G6PD
Mediterranean kinetically but with a slightly rapid electrophoretic
mobility. They demonstrated a G-to-A transition at nucleotide 1361,
producing an arg-to-his substitution.

.0021
G6PD CANTON
G6PD GIFU;;
G6PD AGRIGENTO;;
G6PD TAIWAN-HAKKA
G6PD, ARG459LEU

G6PD Canton is one of the most common deficient variants in Orientals,
reaching a gene frequency of 1.7% in southern China (McCurdy et al.,
1966). Stevens et al. (1990) demonstrated that codon 459 in G6PD-B is
changed from CGT(arginine) to CTT(leucine). The G-to-T change occurs at
nucleotide 1376. Tang et al. (1992) found this mutation in 3 Taiwanese
and 1 Hakkanese in Taiwan. They pointed out that the same mutation
occurs in 3 other Chinese G6PD variants in Guangdong, China:
Taiwan-Hakka (McCurdy et al., 1970), Gifu (Fujii et al., 1984), and
Agrigento (Sansone et al., 1975). The G6PD Gifu variant was discovered
in a 9-year-old Japanese male with chronic hemolysis and hemolytic
crises after upper respiratory infections (Fujii et al., 1984). Enzyme
activity was 2.9% of normal. The patient's G6PD showed increased
utilization of substrate analog, deamino-NADP, and thermal instability.

.0022
G6PD PUERTO LIMON
ANEMIA, NONSPHEROCYTIC HEMOLYTIC, DUE TO G6PD DEFICIENCY
G6PD, GLU398LYS

Beutler et al. (1991) found a G-to-A transition at nucleotide 1192
causing a substitution of the amino acid lysine for the normal glutamic
acid at position 398. This aberrant G6PD associated with nonspherocytic
hemolytic anemia (300908) was described by Elizondo et al. (1982).

.0023
G6PD SANTAMARIA
G6PD, ASP181VAL, ASN126ASP

Beutler et al. (1991) found an A-to-T mutation at nucleotide 542
resulting in an asp-to-val substitution at amino acid 181. The subjects
were white with 'some evidence of hemolysis' in one but none in the
other. This aberrant G6PD, described by Saenz et al. (1984) in 2
unrelated subjects from Costa Rica, is 1 of 4 polymorphic variants that
have 2 point mutations. One of these point mutations in each case is
376A-G (asn126asp), the change characteristic of the nondeficient
polymorphic variant G6PD A- (305900.0002).

.0024
G6PD GASTONIA
G6PD MARION;;
G6PD MINNESOTA;;
ANEMIA, NONSPHEROCYTIC HEMOLYTIC, DUE TO G6PD DEFICIENCY
G6PD, VAL213LEU

Beutler et al. (1991) found that although the patients from whom this
variant G6PD was derived were unrelated, all had a G-to-T mutation at
nucleotide 637 in exon 6 leading to substitution of leucine for
valine-213. The G6PD variants called Gastonia, Marion, and Minnesota
were all from patients with nonspherocytic hemolytic anemia (300908).

.0025
G6PD NASHVILLE
G6PD ANAHEIM;;
ANEMIA, NONSPHEROCYTIC HEMOLYTIC, DUE TO G6PD DEFICIENCY
G6PD, ARG393HIS

In 2 unrelated patients with nonspherocytic hemolytic anemia (300908),
Beutler et al. (1991) found a G-to-A mutation at nucleotide 1178 in exon
10 producing substitution of histidine for arginine-393.

.0026
G6PD VIANGCHAN
G6PD JAMMU
G6PD, VAL291MET

See Poon et al. (1988). Beutler (1991) reported a G-to-A mutation at
nucleotide 871, resulting in substitution of methionine for valine-291.
The variant belonged to WHO class 2.

Louicharoen and Nuchprayoon (2005) and Matsuoka et al. (2005) indicated
that G6PD Viangchan is the most common mutation in the Cambodian
population, similar to Thai and Laotian populations, suggesting a common
ancestry for people from these 3 countries. Matsuoka et al. (2005) found
that G6PD Viangchan was linked in 8 cases with a 1311C-T transition
(305900.0018) in exon 11 and a T-to-C substitution in intron 11, 93 bp
downstream of exon 11. The finding was in accordance with studies of
G6PD Viangchan in Laos, Thailand, and Malaysia.

.0027
G6PD A-
G6PD, ARG227LEU

In subjects with the G6PD A- phenotype, Hirono and Beutler (1988) found
substitution of leucine for arginine-227, resulting from a G-to-T
mutation at nucleotide 680 (rather than the val68-to-met mutation as in
the usual G6PD A-). The mutation existed on the G6PD A background
(asn126 to asp).

.0028
G6PD A-
G6PD, LEU323PRO

In subjects with the G6PD A- phenotype, Hirono and Beutler (1988) found
substitution of proline for leucine-323, resulting from a T-to-C
mutation at nucleotide 968 (rather than the val68-to-met mutation as in
the usual G6PD A-). The mutation existed on the G6PD A background
(asn126-to-asp).

.0029
G6PD KAIPING
G6PD ANANT;;
G6PD DHON;;
G6PD PETRICH-LIKE;;
G6PD SAPPORO-LIKE
G6PD, ARG463HIS

Zuo et al. (1990) demonstrated substitution of histidine for
arginine-463 resulting from a G-to-A mutation in nucleotide 1388. The
G6PD was of the WHO class 2. The Chinese variant G6PD Kaiping was
discovered by Du et al. (1988). The same mutation was found in G6PD
Anant (Panich and Sungnate, 1973), Dhon (Panich and Na-Nakorn, 1980),
Petrich-like (Shatskaya et al., 1980), and Sapporo-like (Fujii et al.,
1981).

.0030
G6PD LOMA LINDA
ANEMIA, NONSPHEROCYTIC HEMOLYTIC, DUE TO G6PD DEFICIENCY
G6PD, ASN363LYS

In a patient with nonspherocytic hemolytic anemia (300908), Beutler et
al. (1991) identified a C-to-A mutation at nucleotide 1089 in exon 10,
producing substitution of asparagine-363 by lysine.

.0031
G6PD COIMBRA
G6PD, ARG198CYS

In the son of a Portuguese woman who had suffered an attack of favism,
Corcoran et al. (1992) identified a G6PD mutant with the chemical
properties of the Mediterranean type (305900.0006). However, at the DNA
level, they demonstrated that the mutation was a C-to-T transition 29
nucleotides downstream from the Mediterranean mutation, resulting in
substitution of cysteine for arginine 10 amino acids downstream from the
Mediterranean change. The same mutation was found in a patient in
southern Italy. The new variant was called G6PD Coimbra.

In 3 individuals with G6PD deficiency from tribal groups in southern
India, Chalvam et al. (2008) identified the Coimbra variant and stated
that the mutation had a frequency of 7.5% in this population.

.0032
CHRONIC GRANULOMA AND HEMOLYTIC ANEMIA
G6PD, SER106CYS, ARG182TRP, ARG198CYS

Gray et al. (1973) described a unique G6PD variant in a patient with
chronic granuloma and hemolytic anemia. G6PD activity was undetectable
not only in the patient's red blood cells but also in leukocytes and
fibroblasts, and an immunologically crossreacting material was
undetectable in these tissues. This is the only variant observed with no
measurable activity and lack of crossreacting material, satisfying the
definition for a 'null' variant. Maeda et al. (1992) found that the mRNA
content and the size of mRNA were normal in the patient's lymphoblastoid
cells (maintained as GM7254 in the Coriell repository in Camden, New
Jersey). Western blot hybridization indicated that the patient's cells
did not produce crossreacting material. Three nucleotide base changes
were found in variant cDNA: a C-to-G transversion at nucleotide 317
(counting from adenine of the initiation codon), which should cause a
ser-to-cys substitution at the 106th position (counting from the
initiation met); a C-to-T transition at nucleotide 544, producing an
arg-to-trp substitution at the 182nd position; and a C-to-T transition
at nucleotide 592, resulting in an arg-to-cys substitution at the 198th
position of the protein. No deletions or frameshift mutations were
found, and no nucleotide change was detected in the extended 5-prime
region which included the most distal cap site. When the variant cDNA
was expressed in E. coli, the G6PD activity was about 2% of normal and
crossreacting material was undetectable. However, when the variant mRNA
was expressed in the in vitro translation system of rabbit
reticulocytes, the variant protein was produced. The results suggested
that extremely rapid in vivo degradation or precipitation of the variant
enzyme induced by the 3 amino acid substitutions could be the major
cause of the molecular deficiency.

.0033
G6PD TAIWAN-HAKKA 2
G6PD, ASN165ASP

Tang et al. (1992) identified an A-to-G transition at nucleotide 493
resulting in an asn165-to-asp amino acid substitution in the G6PD
protein. The biochemical features of the mutation were not
characterized. This mutation has only been reported in Chinese.

The Chinese population of Taiwan is divided into 4 groups: Taiwanese,
mainland Chinese, Hakkanese, and Aborigines. The Taiwanese, the largest
group, are descendants from emigrants who left mainland China during the
17th to 19th centuries. Most were from Fuchien Province on the southeast
coast of China. The second largest population is mainland Chinese, who
resided originally in many provinces throughout mainland China and
migrated to Taiwan during the period 1948 to 1950. The third population
is Hakkanese (Taiwan-Hakka), originally from Chung Yuan, who immigrated
from the Kwangtung and Fuchien provinces on the southern coast of China
and who came to Taiwan primarily during the 16th and 17th centuries. The
native Taiwan Aborigines are a much smaller group, containing at least 9
distinct tribes whose ancestors are believed to have arrived in Taiwan
from mainland Asia several thousand years ago. The frequency of G6PD
deficiency varies from 4.52% in the Hakkanese to an average of 0.3% in
most of the Aborigines. The Ami tribe of Aborigines shows a frequency of
3.5%, presumably a reflection of founder effect.

.0034
G6PD SANTIAGO
ANEMIA, NONSPHEROCYTIC HEMOLYTIC, DUE TO G6PD DEFICIENCY
G6PD, ARG198PRO

In a Chilean patient with nonspherocytic hemolytic anemia (300908),
Beutler et al. (1992) identified a G-to-C transversion at nucleotide 593
leading to an arg198-to-pro substitution. They suggested G6PD Santiago
as the designation. (G6PD Santiago de Cuba is a different mutation; see
305900.0009.)

.0035
G6PD MEXICO CITY
G6PD, ARG227GLN

In a Mexican individual with no clinical features attributable to the
G6PD variant, Beutler et al. (1992) described a G-to-A transition at
nucleotide 680 leading to an arg227-to-gln substitution. They suggested
the designation G6PD Mexico City. (There is a G6PD Mexico; see under
305900.9999.) Nucleotide 680 is the same base that is altered from
G-to-T in one type of G6PD A- (arg227-to-leu).

.0036
G6PD IERAPETRA
G6PD, PRO353SER

In a Greek person with no clinical abnormalities that could be related
to the G6PD variant, Beutler et al. (1992) identified a C-to-T
transition at nucleotide 1057 resulting in a pro353-to-ser substitution.

.0037
G6PD GUADALAJARA
ANEMIA, NONSPHEROCYTIC HEMOLYTIC, DUE TO G6PD DEFICIENCY
G6PD, ARG387CYS

See Vaca et al. (1982). In a Mexican patient with nonspherocytic
hemolytic anemia (300908), Beutler et al. (1992) identified an
arg387-to-cys substitution resulting from a C-to-T transition at
nucleotide 1159.

.0038
G6PD ALHAMBRA
ANEMIA, NONSPHEROCYTIC HEMOLYTIC, DUE TO G6PD DEFICIENCY
G6PD, VAL394LEU

See Beutler and Rosen (1970). Beutler et al. (1992) indicated that the
mutation in this G6PD variant found in a US white patient with
nonspherocytic hemolytic anemia (300908) involved a G-to-C transversion
at nucleotide 1180 resulting in a val394-to-leu substitution.

.0039
G6PD JAPAN
ANEMIA, NONSPHEROCYTIC HEMOLYTIC, DUE TO G6PD DEFICIENCY
G6PD, GLY410ASP

In a Japanese patient with nonspherocytic hemolytic anemia (300908),
Beutler et al. (1992) identified a G-to-A transition at nucleotide 1229
resulting in a gly410-to-asp substitution.

.0040
G6PD PAWNEE
ANEMIA, NONSPHEROCYTIC HEMOLYTIC, DUE TO G6PD DEFICIENCY
G6PD, ARG439PRO

See Prchal (1985). In a US white patient with nonspherocytic hemolytic
anemia (300908), Beutler et al. (1992) identified a G-to-C transition at
nucleotide 1316 leading to an arg439-to-pro substitution.

.0041
G6PD SUNDERLAND
ANEMIA, NONSPHEROCYTIC HEMOLYTIC, DUE TO G6PD DEFICIENCY
G6PD, ILE35DEL

Using a PCR-based technique, MacDonald et al. (1991) determined the
nucleotide sequence of the entire coding region of the G6PD gene from a
person with severe red cell G6PD deficiency and chronic hemolytic anemia
(300908). The only abnormality found was a 3-bp deletion in exon 2,
which predicted the loss of 1 of 2 adjacent isoleucine residues (amino
acid 35 or 36), just upstream of the methionine residue called
'junctional' by Kanno et al. (1989). This part of exon 2 lies in a
region that was thought by Kanno et al. (1989) to be encoded by a gene
on chromosome 6, an idea subsequently disproved. The observations of
MacDonald et al. (1991) demonstrated that a mutation in this X-linked
amino-terminal region of G6PD caused deficiency in red cells. The
deletion was within a 3-fold CAT repeat and had presumably resulted from
misalignment at meiosis, with conservation of the reading frame.

.0042
G6PD KERALA-KALYAN
G6PD KERALA;;
G6PD KALYAN
G6PD, GLU317LYS

G6PD Kerala (Azevedo et al., 1968) and G6PD Kalyan (Ishwad and Naik,
1984), 2 variants discovered in India, were thought to be distinct on
the basis of their biochemical properties. Ahluwalia et al. (1992)
demonstrated that the molecular defect is identical. Both have a
glu317-to-lys mutation which causes a loss of 2 negative charges; this
is in keeping with the very slow electrophoretic mobility of G6PD
Kerala-Kalyan. Both are accompanied by only mild enzyme deficiency. In
both, the mutation is a C-to-T transition in the CpG dinucleotide. The
mutations were found in 2 populations that are entirely distinct
linguistically and culturally with no known historical links. However,
in light of the traditional occupation of the Koli tribal group
inhabiting the Kalyan district of Bombay, namely, marine fishing,
victims of bad weather may have found their way to distant places where
they were forced to live for some period, thus creating the possibility
of gene flow.

.0043
G6PD AURES
G6PD, ILE48THR

In an Algerian boy who presented to the hospital with acute hemolytic
anemia associated with 7 to 10% of G6PD residual activity, Nafa et al.
(1993) identified a T-to-C transition at nucleotide 143 converting codon
48 from ATC (ile) to ACC (thr). The mutation was associated with favism.

In Saudi Arabia, Niazi et al. (1996) described G6PD Aures in 7 of 20
children (35%) with severe G6PD deficiency and in a 16-year-old boy with
a history of passing dark urine after eating fava beans at the age of 5
years. Of the 20 children, 12 were positive for G6PD Mediterranean
(305900.0006), and the mutation in 1 child remained unidentified.

.0044
G6PD GAOHE
G6PD, HIS32ARG

This G6PD variant was described by Du et al. (1985). Its biochemical
characterization was reviewed by Chiu et al. (1993), who demonstrated
that the mutant is frequent in Chinese and consists of a change in cDNA
nucleotide 95 from A to G (his to arg).

.0045
G6PD QUING YUAN
G6PD, GLY131VAL

In an analysis of the molecular defect in 43 G6PD-deficient Chinese,
Chiu et al. (1993) found 3 with a G-to-T transversion in cDNA nucleotide
392 (exon 5) resulting in a gly-to-val substitution. They reviewed the
biochemical characteristics of this previously unidentified variant.

.0046
G6PD MAHIDOL-LIKE
G6PD, LEU342PHE

In a study of the molecular defect in 43 G6PD-deficient Chinese, Chiu et
al. (1993) identified a 'new' variant due to a C-to-T transition at cDNA
nucleotide 1024 resulting in a leu-to-phe substitution. Chiu et al.
(1993) listed the biochemical characteristics of G6PD Mahidol-like.

.0047
G6PD ORISSA
G6PD, ALA44GLY

To determine the extent of heterogeneity of G6PD in India, Kaeda et al.
(1995) studied several different Indian populations by screening for
G6PD deficiency, followed by molecular analysis of deficient alleles.
The frequency of G6PD deficiency varied between 3% and 15% in different
tribal and urban groups. Remarkably, a previously unreported deficient
variant, G6PD Orissa (ala44-to-gly), was found to be responsible for
most of the G6PD deficiency in tribal Indian populations but was not
found in urban populations where most of the G6PD deficiency was due to
the G6PD Mediterranean (ser188-to-phe) variant (305900.0006). The
distribution of G6PD alleles in India is reminiscent of the situation
found with beta-globin (141900), as reviewed by Nagel and Ranney (1990).
In that case, sickle cell anemia is almost entirely restricted to the
tribal groups, whereas urban populations have a predominance of
beta-thalassemia mutations. Kaeda et al. (1995) noted that the Km(NADP)
of G6PD Orissa was 5-fold higher than that of the normal enzyme. This
was thought to be due to the fact that the alanine residue that is
replaced by glycine is part of a putative coenzyme-binding site.
Surprisingly, the enzyme appeared to the authors to be more stable than
normal G6PD, whereas most deficient variants have lowered stability.

.0048
G6PD NANKANG
G6PD, PHE173LEU

In a Chinese newborn with neonatal jaundice, Chen et al. (1996)
identified a novel G6PD mutation, G6PD NanKang, caused by a T-to-C
transition at nucleotide 517, producing a phe173leu substitution in the
G6PD protein.

.0049
G6PD MALAGA
G6PD, ASP181VAL

In a study of G6PD-deficient patients who presented with clinical favism
in Spain, Vulliamy et al. (1996) found a new polymorphic variant they
called G6PD Malaga, whose only abnormality was an A-to-T transversion at
nucleotide 542 resulting in an asp181-to-val amino acid substitution.
This was the same mutation previously found in association with the
mutation of G6PD A-, namely asn126asp (305900.0001) in the double mutant
G6PD Santamaria (305900.0023). G6PD Malaga was associated with enzyme
deficiency class 3, and the enzymic properties of G6PD Malaga and G6PD
Santamaria were quite similar. Vulliamy et al. (1996) speculated that
G6PD Santamaria might have been produced by recombination between G6PDA
and G6PD Malaga; however, haplotype analysis, including the use of a new
silent polymorphism, suggested that the same 542A-T mutation had taken
place independently in a G6PD B gene to give G6PD Malaga and in a G6PD A
gene to give G6PD Santamaria.

.0050
G6PD NEAPOLIS
G6PD, PRO467ARG

In a study of 31 unrelated G6PD-deficient males in the Campania region
of Southern Italy, Alfinito et al. (1997) found 9 different G6PD
variants, 8 of which had already been described. The new variant, G6PD
Neapolis, was found to have a pro467-to-arg substitution in the G6PD
protein.

.0051
G6PD SERRES
ANEMIA, NONSEPHEROCYTIC HEMOLYTIC, DUE TO G6PD DEFICIENCY
G6PD, ALA361VAL

In a study of the causative mutation in 12 cases of G6PD deficiency
associated with chronic nonspherocytic hemolytic anemia (300908),
Vulliamy et al. (1998) found 1 patient to have a novel mutation, which
they called G6PD Serres: a 1082C-T change, causing an ala361-to-val
substitution in the dimer interface where most other severe G6PD
mutations are found.

.0052
G6PD NARA
ANEMIA, NONSEPHEROCYTIC HEMOLYTIC, DUE TO G6PD DEFICIENCY
G6PD, 24-BP DEL, NT953

In a Japanese boy with severe G6PD deficiency (300908), Hirono et al.
(1998) identified a 24-bp deletion (nucleotides 953-976) in exon 9 of
the G6PD gene, which predicted an 8-amino acid deletion at residue 319.

.0053
G6PD AVEIRO
ANEMIA, NONSPHEROCYTIC HEMOLYTIC, DUE TO G6PD DEFICIENCY
G6PD, CYS269TYR

In a boy born in Aveiro, Portugal with severe chronic hemolytic anemia
(300908) present from birth, Costa et al. (2000) found that the
undetectable G6PD activity was caused by a G-to-A transition at
nucleotide position 806 of the G6PD gene resulting in a cys269-to-tyr
(C269Y) amino acid substitution. This mutation, which was designated
G6PD Aveiro, was not detected in his mother or sister. By the age of 5
years, the patient had had 6 episodes of severe acute intravascular
hemolysis that required hospitalization and erythrocyte transfusion. The
spleen was palpable 6 cm below the left costal margin. Costa et al.
(2000) pointed out that G6PD mutants causing class 1 variants (the most
severe forms of the disease) cluster within exon 10, in a region that,
at the protein level, is believed to be involved in dimerization. The
mutation in this new class 1 variant maps to exon 8. Mutant and normal
alleles were found in both hematopoietic and buccal cells, indicating
mosaicism.

.0054
G6PD ASAHI
G6PD, VAL68MET

G6PD A- is a common G6PD variant among Africans that may cause acute
hemolysis triggered by infections and certain drugs, as well as by fava
beans. This class 3 phenotype can be caused by a combination of the
common 376A-G (asn126 to asp) mutation and either of 3 additional
mutations that include 202G-A (val68 to met); see 305900.0002. The
missense mutation 376A-G (asn126 to asp) by itself causes an
asymptomatic class 4 variant G6PD A with normal enzyme activity, whereas
the other mutation, 202G-A, had not been found in humans by itself.
Hirono et al. (2002) described an asymptomatic G6PD-deficient patient
with the missense mutation 202G-A but not the 376A-G. This was a
3-year-old Japanese boy who was noted to have jaundice and anemia on
admission to the Asahi General Hospital. This was the only mutation
found and it must have arisen separately from those common in Africans,
because the patient had none of the silent mutations closely linked to
the African mutation, while he had an intronic single base deletion
common in Mongoloids. Town et al. (1992) had found in an in vitro study
using recombinant human G6PD mutants expressed in E. coli that 202G-A,
as well as 376A-G, does not cause enzyme deficiency by itself, and the
synergistic action of these 2 mutations is necessary to produce the
class 3 phenotype of G6PD A-. Synergistic interaction was also supported
by the fact that val68 and asn126 are closely located in a 3-dimensional
model of human G6PD. The results of Hirono et al. (2002) seem
inconsistent with the idea that 202G-A cannot produce acute hemolysis by
itself.

.0055
G6PD REHOVOT
ANEMIA, NONSPHEROCYTIC HEMOLYTIC, DUE TO G6PD DEFICIENCY
G6PD, TYR322HIS

In 3 brothers and their carrier mother of Jewish Ethiopian descent,
Iancovici-Kidon et al. (2000) found a T-to-C transition at nucleotide
964 in exon 9 of the G6PD gene, resulting in a tyr322-to-his (Y322H)
mutation. All 3 sibs showed hereditary nonspherocytic hemolytic anemia
(300908), but the severity of hemolysis and the transfusion requirement
varied markedly. One brother had severe congenital neutropenia (SCN;
202700), a condition not previously described in association with G6PD
deficiency. Levels of white blood cell G6PD activity of the 3 sibs was 0
to 5% of normal controls. Neutrophil oxidative and bactericidal
activities were impaired in the brother with SCN, but were well
preserved in the other 2 sibs.

.0056
G6PD AMSTERDAM
ANEMIA, NONSPHEROCYTIC HEMOLYTIC, DUE TO G6PD DEFICIENCY
G6PD, 3-BP DEL, 180TCT

In a study of blood cells of 4 male patients from 2 unrelated families
with nonspherocytic anemia (300908) and recurrent bacterial infections,
van Bruggen et al. (2002) discovered that the activity of G6PD in red
blood cells and in granulocytes was below detection level. Moreover,
their granulocytes displayed a decreased respiratory burst upon
activation. Sequencing of genomic DNA revealed a novel 3-bp (TCT)
deletion in the G6PD gene, predicting the deletion of a leucine at
position 61. The mutant G6PD protein was undetectable by Western
blotting in red blood cells and granulocytes of these patients. In
phytohemagglutinin-stimulated lymphocytes, the G6PD protein was present,
but the amount of the protein was greatly diminished in the patients'
cells. Purified mutant protein from an E. coli expression system showed
decreased heat stability and decreased specific activity. Furthermore,
van Bruggen et al. (2002) demonstrated that mRNA of the mutant G6PD was
unstable, which may contribute to the severe G6PD deficiency observed in
these patients. They proposed the name 'G6PD Amsterdam' for the new
variant.

One family reported by van Bruggen et al. (2002) was Caucasian, the
second was Hindustani. The Caucasian patient had an unremarkable medical
history until he was admitted to the hospital at age 15 years with
recurrent episodes of fever, jaundice, gastroenteritis, and coughing. He
was found to have invasive disseminated aspergillosis (see 614079) in
the lungs, brain, and soft tissues of the leg. Aspergillosis was
successfully treated. Thereafter, hemoglobin level was normal but
reticulocytosis was persistent. One of his brothers also had G6PD
deficiency and presented with prolonged neonatal jaundice and episodes
of acute hemolysis but had no known disposition to infections.

The Hindustani proband reported by van Bruggen et al. (2002) was healthy
until the age of 3.5 years, when he was admitted to the hospital with
pneumonia caused by Chromobacterium violaceum, an uncommon human
pathogen that can cause serious infections in patients with neutrophil
dysfunction. He was anemic. He responded well to chemotherapy, although
the anemia persisted. With relapse he developed osteomyelitis but again
responded to therapy.

.0057
G6PD ZURICH
G6PD, IVS10AS, A-G, -2

In a 33-year-old Swiss male with G6PD deficiency, designated G6PD
Zurich, Efferth et al. (2004) identified a single nucleotide mutation
that altered position -2 of intron 10 of the G6PD gene from the
consensus A to G. The mutation resulted in alternative splicing that
removed the first 9 nucleotides of exon 11, which code for amino acids
asparagine, valine, and lysine at positions 430-432, respectively.
Efferth et al. (2004) estimated that 400 million people worldwide are
affected by G6PD deficiency, the most common hereditary enzymopathy,
with some 140 known molecular G6PD defects. They pointed out that most
mutations in the G6PD gene are missense mutations. To the best of their
knowledge, there was only 1 missplicing mutation previously described:
G6PD Varnsdorf (305900.0058), which is caused by destruction of the same
obligate splice site as that destroyed in G6PD Zurich. In G6PD
Varnsdorf, the invariant 3-prime AG dinucleotide has been deleted,
whereas in G6PD Zurich, a point mutation has changed AG to GG. In both
G6PD Zurich and G6PD Varnsdorf, the next available downstream consensus
splice sequence is used, resulting in deletion of 3 amino acids. Efferth
et al. (2004) suggested that it was no coincidence that the only 2
splicing mutations of G6PD identified to that time both affected the
same splice site. Since null mutations of G6PD appear to be incompatible
with life, a functional alternative splice site that does not cause a
frameshift is required for viability. The 3-prime splice site of intron
10 offers this opportunity.

.0058
G6PD VARNSDORF
G6PD, IVS10AS, 2-BP DEL, AG, -2

See 305900.0057 and Efferth et al. (2004).

.0059
G6PD COSENZA
G6PD, ARG459PRO

Calabro et al. (1993) identified a novel G6PD variant, which they called
Cosenza, in patients with G6PD deficiency from the Calabria region of
southern Italy. The arg459-to-pro (A459P) substitution results from a
1376G-C transversion. The mutant protein retains less than 10% enzyme
activity and belongs to the group of severe disorders often associated
with hemolysis.

Barisic et al. (2005) identified G6PD Cosenza in 9 (37.5%) of 24
unrelated patients with G6PD deficiency from the Dalmatian region of
southern Croatia. Seven of the 9 patients had favism.

.0060
G6PD SPLIT
G6PD, PRO481ARG

In a male with G6PD deficiency from the Dalmatian region of southern
Croatia, Barisic et al. (2005) identified a 1442C-G transversion in the
G6PD gene, resulting in a pro481-to-arg (P481R) substitution. The mutant
protein retained approximately 30% enzyme activity (class 3).

.0061
G6PD NAMORU
G6PD, HIS70TYR

Chalvam et al. (2006) identified a 208T-C transition in exon 4 of the
G6PD gene, resulting in a his70-to-tyr (H70Y) substitution, as the basis
of G6PD deficiency in Indian patients with the disorder. The H70Y
mutation was detected in 28 (70.4%) of 40 affected Indian males from 3
tribal groups from the Nilgiri district of Tamil Nadu in southern India.
The variant was termed G6PD Namoru.

.0062
G6PD NILGIRI
G6PD, ARG198HIS

In 4 individuals with G6PD deficiency from tribal groups of the Nilgiri
district in southern India, Chalvam et al. (2008) identified a 593G-A
transition in exon 6 of the G6PD gene, resulting in an arg198-to-his
(R198H) substitution, which they designated G6PD Nilgiri. The authors
stated that the mutation had a frequency of 10.0% in this population.

.9999
GLUCOSE-6-PHOSPHATE DEHYDROGENASE VARIANTS, MOLECULAR DEFECT UNKNOWN
G6PD VARIANTS, MOLECULAR DEFECT UNKNOWN

The following list of G6PD variants which have not been characterized at
the molecular level is in alphabetic order. Quotation marks surround the
name of each G6PD variant about which there is insufficient information
for certainty of its uniqueness.

G6PD AACHEN. See Kahn et al. (1976).

G6PD AARAU. See Gahr et al. (1976).

G6PD 'ABEOKUTA'. See Usanga et al. (1977).

G6PD ABRAMI. See Kahn et al. (1975).

G6PD 'ADAME'. See Usanga et al. (1977). G6PD ADANA. See Aksoy et al.
(1987).

G6PD AKITA. See Miwa et al. (1978).

G6PD ALABAMA. Prchal et al. (1988) described a 6-year-old black boy who
had transient hemolysis after a viral infection and was found to have
mildly decreased red cell G6PD activity. The unusual finding was the
presence of 2 G6PD bands in him and in his maternal grandfather despite
normal XY karyotype. Two bands were seen only in reticulocytes. Prchal
et al. (1988) postulated that there were 2 transcriptional products of
the mutant G6PD gene, 1 of which had a short half-life and was
detectable only in young red blood cells.

G6PD ALBUQUERQUE. See Beutler et al. (1968).

G6PD ALESSANDRIA. Similar to G6PD Alexandra. See Sansone et al. (1981).

G6PD ALEXANDRA. This was found in Australia in a male of Italian
extraction who suffered severe neonatal jaundice following maternal
ingestion of fava beans prenatally and postnatally. Retesting in
adolescence showed milder expression of the enzyme defect (Harley et
al., 1978).

G6PD ALGER. See Benabadji et al. (1978).

G6PD AMBOIN. See Chockkalingam et al. (1982).

G6PD AMMAN-1. See Karadsheh et al. (1986).

G6PD AMMAN-2. See Karadsheh et al. (1986).

G6PD ANGORAM. See Chockkalingam et al. (1982).

G6PD ANKARA. See Kahn et al. (1975).

G6PD ARLINGTON HEIGHTS. See Honig et al. (1979).

G6PD ASAHIKAWA. This variant was discovered in a 6-year-old Japanese boy
with chronic hemolytic anemia and hemolytic crises after upper
respiratory infections (Takizawa et al., 1984).

G6PD ASHDOD. See Ramot et al. (1969).

G6PD ATHENS. See Stamatoyannopoulos et al. (1967).

G6PD 'ATHENS-LIKE'. See Stamatoyannopoulos et al. (1971).

G6PD ATLANTA. See Beutler et al. (1976).

G6PD 'ATTICA'. See Rattazzi et al. (1969).

G6PD AVENCHES. See Pekrun et al. (1989).

G6PD 'AVVOCATA'. See Colonna-Romano et al. (1985).

G6PD AYUTTHAYA. See Panich (1980).

G6PD AZERBAIJAN. See Shatskaya et al. (1975).

G6PD B. The so-called normal, this form predominates in all populations
greater than a few hundred (Yoshida et al., 1971).

G6PD 'BAGDAD'. See Geerdink et al. (1973).

G6PD BAKU. See Shatskaya et al. (1980). G6PD 'BALCALI'. See Aksoy et al.
(1987).

G6PD BALI. See Chockkalingam et al. (1982).

G6PD BALTIMORE-AUSTIN. See Porter et al. (1964) and Long et al. (1965).

G6PD BANGKOK. See Talalak and Beutler (1969).

G6PD BARBIERI. See Marks et al. (1962).

G6PD BARCELONA. See Vives-Corrons et al. (1982). This is one of the rare
G6PD variants associated with granulocyte dysfunction and increased
susceptibility to infections. Hemolysis in this form of chronic
nonspherocytic hemolytic anemia is exaggerated by infection.

G6PD 'BASH-KUNGUT I AND II'. See Shatskaya et al. (1980).

G6PD 'BASH-KUNGUT IV'. See Shatskaya et al. (1980).

G6PD BAT-YAM. See Ramot et al. (1969).

G6PD BAUDELOCQUE. See Junien et al. (1974). G6PD 'BEAUJON'. See Boivin
and Galand (1968).

G6PD BEAUMONT. Mamlok et al. (1985) reported a new molecular variant
associated with severe enzyme deficiency and chronic nonspherocytic
hemolytic anemia. The characteristics were marked heat lability, a
normal rate constant value for glucose-6-phosphate, a nearly normal pH
activity curve, and increased use of 2-deoxyglucose-6-phosphate. Mamlok
et al. (1987) described a fatal case of Chromobacterium violaceum sepsis
in a 3-year-old boy with this variant. The child was an identical twin;
the surviving twin subsequently had a severe episode of Campylobacter
jejuni gastroenteritis. Patients with severe deficiency of G6PD and
polymorphonuclear leukocytes have increased susceptibility to infections
and abnormal phagocyte function that resembles that of patients with
chronic granulomatous disease, but such had not hitherto been reported
during the first decade of life. Infections with C. violaceum are rare;
most of the 20 or so infections have occurred in Louisiana or Florida
and have been associated with warm, stagnant water sources.

G6PD BENEVENTO. See McCurdy et al. (1973).

G6PD BERLIN. See Helge and Borner (1966).

G6PD BIDEIZ. See Krasnopolskaya et al. (1977).

G6PD BIELEFELD. See Gahr et al. (1977).

G6PD BIRMINGHAM. See Prchal et al. (1980).

G6PD BLIDA. See Benabadji et al. (1978).

G6PD BNEI BRAK. See Sidi et al. (1980).

G6PD BODENSEE. See Benohr et al. (1971).

G6PD BOGIA. See Chockkalingam and Board (1980).

G6PD BOLUO. See Du et al. (1988).

G6PD BOLUO-2. See Du et al. (1988).

G6PD BOSTON. See Necheles et al. (1971).

G6PD BUKITU. See Chockkalingam and Board (1980).

G6PD BUTANTAN. In Brazil, Stocco dos Santos et al. (1991) described a
Gd(+) variant which was characterized by normal activity and
electrophoretic mobility, increased Km, and increased activity for
2-deoxy-G6P. The variant, which they called G6PD Butantan, was present
in 3, and perhaps a fourth, cousin; the 4 mothers were sisters. All 4
males had severe mental retardation, bilateral congenital hip luxation,
and short stature. Five uncles of these males may have been affected. In
this family, Stocco dos Santos et al. (2003) found linkage of the
X-linked mental retardation syndrome (300434) to the pericentric region,
Xp11.3-q21.1.

G6PD 'CAGLIARI II' (CAGLIARI-LIKE). See Frigerio et al. (1987) and
Calabro et al. (1990).

G6PD 'CALTANISSETTA'. See Sansone et al. (1981) and Perroni et al.
(1982).

G6PD 'CAMALDOLI'. See Colonna-Romano et al. (1985).

G6PD CAMPBELLPORE. See McCurdy et al. (1970).

G6PD CAMPERDOWN. Harley et al. (1978) found this variant in Australia in
a boy of Maltese extraction in whom lamellar cataracts were found at age
4. The enzyme deficiency was detected in a screening of children of
Mediterranean extraction with lamellar cataracts. The boy had no
excessive hemolysis. Previous descriptions of cataracts were in patients
with hemolytic anemia.

G6PD CAPETOWN. See Botha et al. (1969).

G6PD CARSWELL. See Siegel and Beutler (1971).

G6PD CASTILLA-LIKE. See Chockkalingam et al. (1982).

G6PD CAUJERI. See Gutierrez et al. (1987).

G6PD CENTRAL CITY. See Csepreghy et al. (1988).

G6PD CHAINAT. See Panich and Na-Nakorn (1980).

G6PD CHAO PHYA. See Panich (1980).

G6PD CHARLESTON. See Beutler et al. (1972).

G6PD CHIAPAS. See Lisker et al. (1978).

G6PD CHIBUTO. See Reys et al. (1970).

G6PD CHICAGO. See Kirkman et al. (1964) and Fairbanks et al. (1980).
Fairbanks et al. (1980) demonstrated that G6PD Chicago and G6PD Cornell
are the same variant; they had been described previously in different
members of a single large kindred.

G6PD CHINESE. See Chan et al. (1972).

G6PD CIUDAD DE LA HABANA. See Gonzalez et al. (1980).

G6PD 'CLICHY'. See Boivin and Galand (1968).

G6PD CLINIC. In a young patient with chronic nonspherocytic hemolytic
anemia and familial amyloidotic polyneuropathy, Vives-Corrons et al.
(1989) identified a new variant with a markedly acidic pH optimum. It
bore some similarity in its molecular characteristics to G6PD Bangkok
and G6PD Duarte.

G6PD COLOMIERS. See Vergnes et al. (1981).

G6PD COLUMBUS. See Pinto et al. (1966).

G6PD CORINTH. Yoshida, A.: unpublished, 1975.

G6PD CORNELL. See Miller and Wollman (1974) and Fairbanks et al. (1980).
Fairbanks et al. (1980) demonstrated that G6PD Chicago and G6PD Cornell
are the same variant; they had been described previously in different
members of a single large kindred.

G6PD CUIABA. In a 33-year-old male of Portuguese extraction who
developed hemolytic anemia after acetaminophen and acetylsalicylic acid
ingestion, Barretto and Nonoyama (1987) found a variant G6PD which had
normal activity and normal electrophoretic mobility, but unusually high
K(m) for glucose-6-phosphate, high K(i) for NADPH, and decreased thermal
stability.

G6PD 'DAKAR'. See Kahn et al. (1971, 1973).

G6PD DALLAS. Beutler, E.; Frenkel, E. P. and Forman, L.: unpublished,
1987.

G6PD DEBROUSSE (G6PD CONSTANTINE, FORMERLY). See Kissin and Cotte (1970)
and Sansone et al. (1975).

G6PD DJYNET. See Krasnopolskaya and Bochkov (1982).

G6PD DOTHAN. See Prchal et al. (1979).

G6PD DUARTE. See Beutler et al. (1968).

G6PD DUBLIN. See McCann et al. (1980).

G6PD DUSHANBA I. See Krasnopolskaya and Bochkov (1982).

G6PD DUSHANBA II. See Krasnopolskaya and Bochkov (1982).

G6PD DUSHANBA III. See Krasnopolskaya and Bochkov (1982).

G6PD EAST AFRICAN. See Othieno-Obel (1972).

G6PD EAST HARLEM. See Feldman et al. (1977).

G6PD 'EKITI'. See Usanga et al. (1977).

G6PD EL-FAYOUM. See McCurdy et al. (1974).

G6PD EL-KHARGA. See McCurdy et al. (1974).

G6PD EL MORRO. See McCurdy et al. (1973).

G6PD ENGLEWOOD. See Rattazzi et al. (1971).

G6PD 'ENSLEY'. See Nsouly and Prchal (1981).

G6PD 'ESPOO'. See Vuopio et al. (1975).

G6PD FERRANDINA. See Calabro et al. (1990).

G6PD FERRARA. See Carandina et al. (1976).

G6PD FERRARA II. See De Flora et al. (1981) and Sansone et al. (1981).

G6PD 'FERRARA III'. See Perroni et al. (1982).

G6PD FORT PIERCE. Phyliky, R. L.; Nishimura, R. A. and Beutler, E.:
unpublished, 1983.

G6PD FORT WORTH. See Mills et al. (1975).

G6PD 'FRANKFURT'. Nowicki et al. (1974).

G6PD FREIBURG. See Weinreich et al. (1968) and Busch and Bote (1970).

G6PD FUKUOKA. This variant was found in a 77-year-old male with
drug-induced hemolysis (Fujii et al., 1984). Enzyme activity was 6.4% of
normal and the patient's G6PD had abnormal electrophoretic mobility and
thermal instability.

G6PD FUKUSHIMA. Miwa et al. (1978) described this 'deficiency' mutant,
which leads to chronic hemolytic anemia. It was slow-moving
electrophoretically, like G6PD Kurume, from which it differed by low
utilization of deamino-NADP and normal pH curve. The proband, a
33-year-old male, had 2.8% of normal enzyme activity and mild hemolytic
anemia. Miwa et al. (1978) stated that 46 variants had previously been
classified as class 1, with severe enzyme deficiency leading to chronic
nonspherocytic hemolytic anemia.

G6PD GABROVIZZA. See Ventura et al. (1984).

G6PD 'GALLIERA'. See Perroni et al. (1982).

G6PD GALLURA. See Sansone et al. (1975).

G6PD 'GALVESTON'. See Alperin and Mills (1972).

G6PD 'GAMBIA'. Welch et al. (1978) found a gene frequency of 0.024 among
1,109 persons examined in The Gambia. This is a slow electrophoretic
variant with reduced enzyme activity.

G6PD GAOMIN. See Du et al. (1988).

G6PD GAOZHOU. See Du et al. (1988).

G6PD GENOVA. See Gaetani et al. (1990).

G6PD GOODENOUGH. See Chockkalingam et al. (1982).

G6PD GOTZE DELCHEV. See Shatskaya et al. (1980). G6PD GRAND PRAIRIE. See
Cederbaum and Beutler (1975).

G6PD GREAT LAKES. Beutler, E. and Maurer, H. S.: unpublished, 1984.

G6PD GUANGZHOU. See Du et al. (1988).

G6PD GUANTANAMO. See Gutierrez et al. (1987). G6PD 'GUIBA'. See Weimer
et al. (1981).

G6PD HAAD YAI. See Panich and Na-Nakorn (1980).

G6PD 'HAMBURG'. See Gahr and Schroeter (1974).

G6PD HAMM. See Gahr et al. (1976).

G6PD 'HANOI'. See Toncheva (1986).

G6PD HAWAII. Beutler, E. and Matsumoto, F.: unpublished, 1975.

G6PD HAYEM. See Kahn et al. (1974). G6PD HEIAN. See Nakai and Yoshida
(1974).

G6PD HEKTOEN. Substitution of tyrosine for histidine (Dern et al.,
1969).

G6PD HELSINKI. See Vuopio et al. (1973) and Harkonen and Vuopio (1974).
Cohn et al. (1979) described severe hemolytic anemia in 2 Danish boys,
who showed deficiency of G6PD. The enzyme had characteristics possibly
identical to those of G6PD Helsinki.

G6PD HILLBROW. See Cayanis et al. (1975).

G6PD 'HIROSHIMA-1'. See Kageoka et al. (1985).

G6PD 'HIROSHIMA-2'. See Kageoka et al. (1985).

G6PD 'HIROSHIMA-3'. See Kageoka et al. (1985).

G6PD HOFU. See Miwa et al. (1977).

G6PD HONG KONG. See Wong et al. (1965) and Chan et al. (1972).

G6PD HONG KONG POKFULAM. See Chan et al. (1972).

G6PD HOTEL DIEU. See Kahn et al. (1977).

G6PD HUALIEN. McCurdy, P. R.: unpublished, 1975.

G6PD HUALIEN-CHI. McCurdy, P. R.: unpublished, 1975.

G6PD HUAZHOU. See Du et al. (1988).

G6PD HUIYANG. See Du et al. (1988).

G6PD HUNTSVILLE. See Hall et al. (1988).

G6PD HURON. See Ravindranath and Beutler (1987).

G6PD IBADAN-AUSTIN. See Long et al. (1965).

G6PD IJEBU-ODE. See Luzzatto and Afolayam (1968).

G6PD INDIANAPOLIS. Beutler, E.; Forman, L. and Gelbart, T.: unpublished,
1985.

G6PD INDONESIA. See Kirkman and Lie-Injo (1969). G6PD INHAMBANE. See
Reys et al. (1970).

G6PD INTANON. See Panich (1974).

G6PD ISERLOHN. Unstable enzyme. See Eber et al. (1985).

G6PD ITA-BALE. See Long et al. (1965).

G6PD IWATE. See Kanno et al. (1987).

G6PD JACKSON. See Thigpen et al. (1974).

G6PD JALISCO. See Vaca et al. (1985).

G6PD JOHANNESBURG. See Balinsky et al. (1973).

G6PD 'JUNUT'. See Shatskaya et al. (1980).

G6PD KABYLE. See Kaplan et al. (1967).

G6PD KALUAN. See Chockkalingam and Board (1980).

G6PD KALUGA. See Shatskaya et al. (1976).

G6PD KAMIUBE. See Nakatsuji and Miwa (1979).

G6PD KAN. See Panich (1973).

G6PD KANAZAWA. This variant, found by Kitao et al. (1982) in a Japanese
male with chronic nonspherocytic hemolytic anemia, has normal
electrophoretic mobility, normal Km for glucose-6-phosphate and NADP,
and normal utilization of the substrate 2-deoxyglucose-6-phosphate and
deamino-NADP. It shows decreased thermal stability and a biphasic pH
curve. G6PD KAR KAR. See Chockkalingam et al. (1982).

G6PD KARDISTA. Stamatoyannopoulos, G.: unpublished, 1975.

G6PD KEPHALONIA. See Rattazzi et al. (1969).

G6PD KEROVOGRAD. See Krasnopolskaya and Bochkov (1982). G6PD 'KHARTOUM'.
See Samuel et al. (1981).

G6PD 'KILGORE'. See Alperin and Mills (1972).

G6PD KING COUNTY. Yoshida, A.: unpublished, 1975.

G6PD KIROVOGRAD. See Shatskaya et al. (1976).

G6PD KIWA. See Nakatsuji and Miwa (1979).

G6PD KOBE. See Fujii et al. (1981).

G6PD KONAN. See Nakatsuji and Miwa (1979).

G6PD KREMENCHUNG. See Chernyak et al. (1977) and Tokarev et al. (1978).

G6PD KUANYAMA. See Balinsky et al. (1974).

G6PD KURUME. A 'deficiency' mutation, this variant leads to chronic
hemolytic anemia. It is electrophoretically slow-moving. The proband was
a 17-year-old male whose red cells had only 0.8% normal enzyme activity
(Miwa et al., 1978). The enzyme showed normal KmG6P, normal KmNADP, low
KiNADP, normal utilization of 2-deoxy-G6P and deamino-NADP, very low
heat stability, and a biphasic pH curve.

G6PD 'KYOTO'. See Kojima (1972). G6PD LAGHOUAT. See Benabadji et al.
(1978).

G6PD LAGUNA. Although the proband was anemic, the absence of anemia in
relatives with the same G6PD variant suggested that the association was
coincidental (Weimer et al., 1984). The characteristics of the mutant
enzyme, including slower electrophoretic mobility, were described.

G6PD 'LANLATE'. See Usanga et al. (1977).

G6PD LAOS. Smith, J. W. and Beutler, E.: unpublished, 1981.

G6PD LAWNDALE. See Grossman et al. (1966).

G6PD LEVADIA. See Stamatoyannopoulos et al. (1970).

G6PD LIFTA. See Ramot et al. (1969).

G6PD LINCOLN PARK. See Honig et al. (1979).

G6PD LINDA VISTA. Smith, J. W. and Beutler, E.: unpublished, 1981.

G6PD 'LIZU-BAISHA'. See Chuanshu et al. (1981).

G6PD LONG PRAIRIE. See Johnson et al. (1977).

G6PD LONG XUYEN. See Panich et al. (1980).

G6PD LOS ANGELES. See Beutler and Matsumoto (1977).

G6PD LOURENZO MARQUES. See Reys et al. (1970). G6PD LOZERE. See Vergnes
et al. (1976).

G6PD LUBLIN. See Pawlak et al. (1970).

G6PD LUZ-SAINT SAUVEUR. See Vergnes et al. (1973).

G6PD LYNN (G6PD YUGOSLAVIA, FORMERLY). Beutler, E. and Lind, S.:
unpublished, 1987.

G6PD MADANG. See Chockkalingam et al. (1982).

G6PD MADISON. See Shows et al. (1964).

G6PD MADRONA. See Hook et al. (1968). G6PD MAINOKI. See Chockkalingam et
al. (1982).

G6PD 'MALI'. See Kahn et al. (1971).

G6PD MAMMOLA. See Perroni et al. (1982).

G6PD MANCHESTER. See Milner et al. (1974).

G6PD MANDANG. See Chockkalingam et al. (1982).

G6PD MANJACAZE. See Reys et al. (1970).

G6PD MANUS. See Chockkalingam et al. (1982).

G6PD MARKHAM. See Kirkman et al. (1968).

G6PD 'MARTINIQUE'. See Kahn et al. (1971).

G6PD MARTINIQUE-LIKE. See Krasnopolskaya et al. (1977).

G6PD MATAM. See Kahn et al. (1975). G6PD MELISSA. Stamatoyannopoulos,
G.: unpublished, 1975.

G6PD MENORCA. See Vives-Corrons and Pujades (1982).

G6PD MERCURY. Beutler, E. and Taylor, G. P.: unpublished, 1982.

G6PD MEXICO. See Lisker et al. (1972).

G6PD MIAOZU-BAISHA. See Du et al. (1984).

G6PD MILWAUKEE. See Westring and Pisciotta (1966).

G6PD MINAS GERAIS. See Azevedo and Yoshida (1969).

G6PD MINNEAPOLIS. Johnson, G. J. and Beutler, E.: unpublished, 1980.

G6PD 'MISENO'. See Colonna-Romano et al. (1985).

G6PD MISSOULA. See Wilson (1976).

G6PD MOOSBURG. See Pekrun et al. (1989).

G6PD MORELIA. Class 4. First in class with a high Km for NADP and a low
Ki for NADPH. See Vaca et al. (1985).

G6PD MOSCOW. See Batischev et al. (1977).

G6PD MURET. See Vergnes et al. (1981).

G6PD MUSASHINO. See Kumakawa et al. (1987).

G6PD NAGANO. This variant is associated with infection-induced hemolysis
and chronic hemolytic anemia due to markedly impaired enzyme activity
and thermal instability (Takahashi et al., 1982).

G6PD 'NAGASAKI-1'. See Kageoka et al. (1985).

G6PD 'NAGASAKI-2'. See Kageoka et al. (1985).

G6PD 'NAGASAKI-3'. See Kageoka et al. (1985).

G6PD 'NANCY'. See Streiff and Vigneron (1971).

G6PD NANHAI. See Du et al. (1988).

G6PD NAPOLI. See De Flora et al. (1981).

G6PD NEDELINO. See Toncheva and Tzoneva (1984).

G6PD NEW GUINEA-II. See Rattazzi et al. (1971).

G6PD NEW YORK. See Rattazzi et al. (1971).

G6PD N-PATHOM. See Panich (1974) and Panich and Na-Nakorn (1980).

G6PD N-SAWAN. See Panich and Na-Nakorn (1980).

G6PD NUCUS. See Yermakov et al. (1981).

G6PD NUHA. See Krasnopolskaya and Bochkov (1982).

G6PD 'NUKHA'. See Shatskaya et al. (1980).

G6PD OGIKUBO. See Miwa et al. (1978).

G6PD OGORI. See Lisker et al. (1977). G6PD OHIO. See Pinto et al.
(1966).

G6PD OKHUT I. See Krasnopolskaya et al. (1977).

G6PD OKHUT II. See Krasnopolskaya et al. (1977).

G6PD OKLAHOMA. See Kirkman and Riley (1961) and Nance (1964).

G6PD ONODA. Nakashima, K.: unpublished, 1978.

G6PD ORCHOMENOS. See Stamatoyannopoulos et al. (1971).

G6PD PADREW. See Panich and Na-Nakorn (1980).

G6PD PALAKAU. See Chockkalingam et al. (1982).

G6PD 'PALEPOLI'. See Colonna-Romano et al. (1985).

G6PD 'PALLONETTO'. See Colonna-Romano et al. (1985). G6PD 'PALMI I'. See
Perroni et al. (1982).

G6PD 'PALMI II'. See Perroni et al. (1982).

G6PD PANAMA. See Beutler et al. (1974).

G6PD PANAY. See Fernandez and Fairbanks (1968).

G6PD PANAY-LIKE.

G6PD 'PARIS'. See Boivin and Galand (1968).

G6PD PEA RIDGE. See Fairbanks et al. (1980).

G6PD 'PETILIA'. See Sansone et al. (1981) and Perroni et al. (1982).

G6PD PETRICH. See Shatskaya et al. (1980).

G6PD PINAR DEL RIO. See Gonzalez et al. (1977).

G6PD PISTICCI. See Viglietto et al. (1990) and Calabro et al. (1990).
G6PD POMPTON PLAINS. Beutler, E.; Davis, S.; Forman, L. and Gelbart, T.:
unpublished, 1985.

G6PD POPONDETTA. See Chockkalingam et al. (1982).

G6PD PORBANDAR. See Cayanis et al. (1977).

G6PD 'PORDENONE'. See Sansone et al. (1981) and Perroni et al. (1982).

G6PD PORT ELIZABETH. See Balinsky et al. (1973).

G6PD PORT-ROYAL. See Kaplan et al. (1971).

G6PD PORTO ALEGRE. See Hutz et al. (1977).

G6PD 'POSILIPPO'. See Colonna-Romano et al. (1985).

G6PD POZNAN. See Pawlak et al. (1975).

G6PD 'POZZALLO'. See Perroni et al. (1982).

G6PD PUERTO RICO. See McCurdy et al. (1973).

G6PD QING-BAILJIANG. See Du et al. (1988).

G6PD RAMAT-GAN. See Ramot et al. (1969).

G6PD REGAR. See Ermakov et al. (1983).

G6PD REGENSBURG. See Eber et al. (1985).

G6PD 'RENNES'. See Picat et al. (1980).

G6PD ROTTERDAM. See Rattazzi et al. (1971).

G6PD RUDOSEM. See Toncheva and Tzoneva (1984).

G6PD RUSSIAN-MOSCOW. See Krasnopolskaya and Bochkov (1982).

G6PD SALATA. See Chockkalingam and Board (1980).

G6PD SAMANDAG. See Aksoy et al. (1987).

G6PD SAN DIEGO. See Howell et al. (1972).

G6PD SAN FRANCISCO. See Mentzer et al. (1980).

G6PD SAN JOSE. See Castro and Snyder (1974).

G6PD SAN JUAN. See McCurdy et al. (1973). G6PD SANTA BARBARA. Kidder, W.
R. and Beutler, E.: unpublished, 1979.

G6PD SAPPORO. See Fujii et al. (1981).

G6PD 'SCHWABEN'. See Benohr et al. (1971).

G6PD 'S.DONA'. See Perroni et al. (1982).

G6PD SEATTLE. See Kirkman et al. (1965).

G6PD SELIM. See Shatskaya et al. (1975).

G6PD SENDAGI. This variant was associated with chronic nonspherocytic
hemolytic anemia in a 2-year-old Japanese male in whom upper respiratory
infection precipitated a hemolytic crisis (Morisaki et al.,1983).

G6PD SHEKII. See Krasnopolskaya et al. (1977). G6PD SHIRIN-BULAKH. See
Krasnopolskaya et al. (1977).

G6PD SIRIRAJ. See Panich et al. (1972).

G6PD SIWA. See McCurdy et al. (1974).

G6PD SONGKHLA. See Panich and Na-Nakorn (1980).

G6PD S-SAKORN. See Panich (1980).

G6PD ST. LOUIS. See Kahn et al. (1974).

G6PD STEILACOM. Yoshida, A.; Baur, E. and Voigtlander, B.: unpublished,
1975.

G6PD 'STELLA'. See Colonna-Romano et al. (1985).

G6PD 'STRASBOURG'. See Waitz et al. (1970).

G6PD SWIT. See Chockkalingam et al. (1982).

G6PD TACOMA. Yoshida, A. and Baur, E.: unpublished, 1975.

G6PD TACOMA-LIKE. See Vergnes et al. (1975).

G6PD TAHTA. See McCurdy et al. (1974).

G6PD TAIPEI-HAKKA. See McCurdy et al. (1970).

G6PD 'TAIWAN-AMI 5'. See McCurdy et al. (1970).

G6PD 'TAIWAN-AMI 6'. See McCurdy et al. (1970).

G6PD TARSUS. See Gahr et al. (1976).

G6PD TASHKENT. See Yermakov et al. (1981).

G6PD TEHERAN. McCurdy, P. R.: unpublished, 1965.

G6PD TEL HASHOMER. See Ramot and Brok (1964) and Kirkman et al. (1969).

G6PD TENGANAN. See Chockkalingam et al. (1982).

G6PD THENIA. See Benabadji et al. (1978).

G6PD THESSALONIKI. Koliakos et al. (1989) found a new variant in a
70-year-old patient with idiopathic myelofibrosis. This disorder,
formerly called agnogenic myeloid metaplasia, is a myeloproliferative
disease with clonal origin in a malignant pluripotent stem cell. Bone
marrow fibrosis is a secondary process. The patient was thought to be
heterozygous since her only son had normal G6PD. That she showed severe
G6PD deficiency was taken to indicate that the normal X chromosome was
active in the original cell that underwent malignancy.

G6PD THESSALY. See Stamatoyannopoulos et al. (1970).

G6PD TITTERI. See Benabadji et al. (1978).

G6PD TITUSVILLE. Csepreghy et al. (1989) described a new G6PD variant in
a 7-month-old black male and his mother. The proband had had a transient
hemolytic episode.

G6PD TOKUSHIMA. See Miwa et al. (1976).

G6PD TOKYO. See Miwa et al. (1976).

G6PD TORONTO. See Crookston et al. (1973).

G6PD TORRANCE. See Tanaka and Beutler (1969).

G6PD TOULOUSE. See Vergnes et al. (1974). G6PD 'TRAPANI'. See Sansone et
al. (1981) and Perroni et al. (1982).

G6PD TRINACRIA. See Sansone et al. (1977).

G6PD TRIPLER. See Engstrom and Beutler (1970).

G6PD TSUKUI. See Ogura et al. (1988).

G6PD TUBINGEN. See Benohr and Waller (1970).

G6PD TURSI. See Viglietto et al. (1990) and Calabro et al. (1990).

G6PD UBE. See Nakashima et al. (1977).

G6PD UNION. See Yoshida et al. (1970).

G6PD 'UNION-MARKHAM'. See Stamatoyannopoulos et al. (1971).

G6PD 'UNNAMED'. See Othieno-Obel (1972).

G6PD 'VARADERO'. See Estrada et al. (1982).

G6PD VELLETRI. See Mandelli et al. (1977).

G6PD VIENTIANE. See Kahn et al. (1978).

G6PD 'VIN FU'. See Toncheva (1986).

G6PD WAKAYAMA. This variant was found in a 16-month-old boy with 4.5% of
normal enzyme activity and mild hemolytic anemia (Miwa et al., 1978).
Electrophoretically, it is slow-moving like G6PD Kurume, from which it
differs by a normal pH curve. In addition to the 4 slow variants
reported by Miwa et al. (1978), 5 had previously been reported:
Alhambra, Atlanta, Hong Kong Pokfulam, Manchester, and Tokyo. G6PD
WASHINGTON. McCurdy, P. R.: unpublished, 1975.

G6PD WATERLOO. Beutler, E. and Phyliky, R. L.: unpublished, 1978.

G6PD WAYNE. See Ravindranath and Beutler (1987). G6PD WEST BENGAL. See
Azevedo et al. (1968).

G6PD WEST TOWN. This variant causes chronic nonspherocytic anemia which
is compensated except following infections or exposure to an oxidant
drug (Honig et al., 1979).

G6PD WESTERN. Yoshida, A. and Baur, E.: unpublished, 1975.

G6PD WEWAK. See Chockkalingam et al. (1982).

G6PD WORCESTER. Snyder et al. (1970) described a family in which a new
variant form of G6PD was associated with congenital nonspherocytic
hemolytic anemia and optic atrophy in 3 males related as first cousins
once removed. Blindness developed rapidly in the teens.

G6PD 'WROCLAW'. See Kwiatkowska and Kacprzak-Bergman (1971).

G6PD YAMAGUCHI. This variant was found in an 8-year-old boy who had 3.5%
of normal enzyme activity and moderate hemolytic anemia (Miwa et al.,
1978). Electrophoretically, it is slow-moving, like G6PD Kurume, from
which it differs by high Km NADP, high deamino-NADP utilization, and an
abnormal pH curve of a different type (with narrow peak at pH 8.76).
G6PD YANGORU. See Chockkalingam et al. (1982).

G6PD YOKOHAMA. See Miwa et al. (1978).

G6PD 'ZAEHRINGEN'. See Witt and Yoshioka (1972).

G6PD ZAKATALY. See Krasnopolskaya et al. (1977).

G6PD ZHITOMIR. See Shatskaya et al. (1976).

*FIELD* SA
Balinsky et al. (1973); Benohr et al. (1971); Beutler (1975); Beutler
and Kuhl (1990); Beutler et al. (1991); Beutler et al. (1991); Boyer
et al. (1962); Cazzola and Bergamaschi (1998); Chan and Todd (1972);
Chang et al. (1992); Chockkalingam et al. (1982); Cooper et al. (1975);
Corash et al. (1980); Epstein (1969); Fiorelli et al. (1989); Fite
et al. (1983); Francke et al. (1974); Friedman and Trager (1981);
Gahr et al. (1976); Gourdin et al. (1972); Hirono and Beutler (1989);
Johnston et al. (1975); Kahn et al. (1975); Kahn et al. (1975); Kirkman
et al. (1964); Kirkman et al. (1964); Luzzatto (1974); Martin et
al. (1979); McCurdy (1971); McCurdy and Mahmood (1970); McCurdy et
al. (1973); Meloni et al. (1990); Miwa et al. (1978); Modiano et al.
(1979); Morisaki et al. (1983); O'Brien (1980); Panich (1974); Panich
et al. (1972); Persico et al. (1981); Persico et al. (1986); Porter
et al. (1962); Roth et al. (1983); Shatskaya et al. (1976); Shatskaya
et al. (1980); Shows and Brown (1975); Stamatoyannopoulos et al. (1970);
Takizawa et al. (1987); Toniolo et al. (1988); Yoshida (1967); Yoshida
(1967)
*FIELD* RF
1. Adam, A.; Tippett, P.; Gavin, J.; Noades, J.; Sanger, R.; Race,
R. R.: The linkage relation of Xg to G6PD in Israelis: the evidence
of a second series of families. Am. J. Hum. Genet. 30: 211-218,
1967.

2. Ahluwalia, A.; Corcoran, C. M.; Vulliamy, T. J.; Ishwad, C. S.;
Naidu, J. M.; Argusti, A.; Stevens, D. J.; Mason, P. J.; Luzzatto,
L.: G6PD Kalyan and G6PD Kerala; two deficient variants in India
caused by the same 317 glu-to-lys mutation. Hum. Molec. Genet. 1:
209-210, 1992.

3. Aksoy, K.; Yuregir, G. T.; Dikmen, N.; Unlukurt, I.: Three new
G6PD variants, G6PD Adana, G6PD Samandag, and G6PD Balcali in Cukurova,
Turkey. Hum. Genet. 76: 199-201, 1987.

4. Alfinito, F.; Cimmino, A.; Ferraro, F.; Cubellis, M. V.; Vitagliano,
L.; Francese, M.; Zagari, A.; Rotoli, B.; Filosa, S.; Martini, G.
: Molecular characterization of G6PD deficiency in Southern Italy:
heterogeneity, correlation genotype-phenotype and description of a
new variant (G6PD Neapolis). Brit. J. Haemat. 98: 41-46, 1997.

5. Alperin, J. B.; Mills, G. C.: New variants of glucose-6-phosphate
dehydrogenase (G6PD). Clin. Res. 20: 76, 1972.

6. Azevedo, E.; Kirkman, H. N.; Morrow, A. C.; Motulsky, A. G.: Variants
of red cell glucose-6-phosphate dehydrogenase among Asiatic Indians. Ann.
Hum. Genet. 31: 373-379, 1968.

7. Azevedo, E. S.; Yoshida, A.: Brazilian variant of glucose-6-phosphate
dehydrogenase (GD Minas Gerais). Nature 222: 380-382, 1969.

8. Babalola, A. O. G.; Beetlestone, J. G.; Luzzatto, L.: Genetic
variants of human erythrocyte glucose-6-phosphate dehydrogenase: kinetic
and thermodynamic parameters of variants A, B, and A- in relation
to quaternary structure. J. Biol. Chem. 251: 2993-3002, 1976.

9. Balinsky, D.; Cayanis, E.; Carter, G.; Jenkins, T.; Bersohn, I.
: A new variant of human erythrocyte glucose-6-phosphate dehydrogenase:
G6PD Port Elizabeth. Int. J. Biochem. 4: 235-244, 1973.

10. Balinsky, D.; Gomperts, E.; Cayanis, E.; Jenkins, T.; Bryer, D.;
Bersohn, I.; Metz, J.: Glucose 6-phosphate dehydrogenase Johannesburg:
a new variant with reduced activity in a patient with congenital non-spherocytic
haemolytic anaemia. Brit. J. Haemat. 25: 385-392, 1973.

11. Balinsky, D.; Rootman, A. J.; Nurse, G. T.; Cayanis, E.; Lane,
A.; Jenkins, T.; Bersohn, I.: G6PD Kuanyama: a new variant of human
erythrocyte glucose 6-phosphate dehydrogenase showing slower than
normal electrophoretic mobility. S. Afr. J. Med. Sci. 39: 5-13,
1974.

12. Barisic, M.; Korac, J.; Pavlinac, I.; Krzelj, V.; Marusic, E.;
Vulliamy, T.; Terzic, J.: Characterization of G6PD deficiency in
southern Croatia: description of a new variant, G6PD Split. J. Hum.
Genet. 50: 547-549, 2005.

13. Barretto, O. C.; Nonoyama, K.: Gd(+) Cuiaba, a new rare glucose-6-phosphate
dehydrogenase variant presenting normal activity. Hum. Genet. 77:
201-202, 1987.

14. Batischev, A. I.; Chernyak, N. B.; Torakev, Y. N.: Detection
of a new abnormal variant of glucose-6-phosphate dehydrogenase in
human red cells. Bulleten Eksperimental Noi Biologii I Meditsiny 84:
728-731, 1977.

15. Ben-Bassat, J.; Ben-Ishay, D.: Hereditary hemolytic anemia associated
with glucose-6-phosphate dehydrogenase deficiency (Mediterranean type). Isr.
J. Med. Sci. 5: 1053-1059, 1969.

16. Benabadji, M.; Merad, F.; Benmoussa, M.; Trabuchet, G.; Junien,
C.; Dreyfus, J. C.; Kaplan, J. C.: Heterogeneity of glucose-6-phosphate
dehydrogenase deficiency in Algeria. Hum. Genet. 40: 177-184, 1978.

17. Benohr, H. C.; Klumpp, F.; Waller, H. D.: Glucose-6-phosphat-Dehydrogenase
Typ Schwaben. Dtsch. Med. Wschr. 96: 1029-1032, 1971.

18. Benohr, H. C.; Waller, H. D.: Eigenschaften der Glucose-6-p-dehydrogenase,
Typ Tubingen. Klin. Wschr. 48: 71-74, 1970.

19. Benohr, H. C.; Waller, H. D.; Arnold, H.; Blume, K. G.; Lohr,
G. W.: Glucose-6-P-Dehydrogenase Typ Bodensee (eine neue Enzymvariante). Klin.
Wschr. 49: 1058-1062, 1971.

20. Beutler, E.: Glucose 6-phosphate dehydrogenase deficiency, a
new Indian variant, G6PD Jammu.In: Sen, N. N.; Basu, A. K.: Trends
in Haematology. Calcutta: Chatterjea Memorial Committee (pub.)
1975. Pp. 279-283.

21. Beutler, E.: Selectivity of proteases as a basis for tissue distribution
of enzymes in hereditary deficiencies. Proc. Nat. Acad. Sci. 80:
3767-3768, 1983.

22. Beutler, E.: Glucose-6-phosphate dehydrogenase deficiency. New
Eng. J. Med. 324: 169-174, 1991.

23. Beutler, E.; Grooms, A. M.; Morgan, S. K.; Trinidad, F.: Chronic
severe hemolytic anemia due to G-6-PD Charleston: a new deficiency
variant. J. Pediat. 80: 1005-1009, 1972.

24. Beutler, E.; Hartman, K.; Gelbart, T.; Forman, L.: G-6-PD Walter
Reed: possible insight into 'structural' NADP in G-6-PD. Am. J. Hemat. 23:
25-30, 1986.

25. Beutler, E.; Keller, J. W.; Matsumoto, F.: A new glucose 6-phosphate
dehydrogenase (G6PD) variant associated with nonspherocytic hemolytic
anemia: G6PD Atlanta. I.R.C.S. 4: 479, 1976.

26. Beutler, E.; Kuhl, W.: Linkage between a PvuII restriction fragment
length polymorphism and G6PD A- (202A/376G): evidence for a single
origin of the common G6PD A- mutation. Hum. Genet. 85: 9-11, 1990.

27. Beutler, E.; Kuhl, W.: The NT 1311 polymorphism of G6PD: G6PD
Mediterranean mutation may have originated independently in Europe
and Asia. Am. J. Hum. Genet. 47: 1008-1012, 1990.

28. Beutler, E.; Kuhl, W.; Gelbart, T.; Forman, L.: DNA sequence
abnormalities of human glucose-6-phosphate dehydrogenase variants. J.
Biol. Chem. 266: 4145-4150, 1991.

29. Beutler, E.; Kuhl, W.; Ramirez, E.; Lisker, R.: Some Mexican
glucose-6-phosphate dehydrogenase variants revisited. Hum. Genet. 86:
371-374, 1991.

30. Beutler, E.; Kuhl, W.; Saenz, G. F.; Rodriguez, W.: Mutation
analysis of glucose-6-phosphate dehydrogenase (G6PD) variants in Costa
Rica. Hum. Genet. 87: 462-464, 1991.

31. Beutler, E.; Mathai, C. K.; Smith, J. E.: Biochemical variants
of glucose-6-phosphate dehydrogenase giving rise to congenital nonspherocytic
hemolytic disease. Blood 31: 131-150, 1968.

32. Beutler, E.; Matsumoto, F.: A new glucose 6-phosphate dehydrogenase
variant: G6PD (-) Los Angeles. I.R.C.S. 5: 89, 1977.

33. Beutler, E.; Matsumoto, F.; Daiber, A.: Nonspherocytic hemolytic
anemia due to G-6-PD Panama. I.R.C.S. 2: 1389, 1974.

34. Beutler, E.; Rosen, R.: Nonspherocytic congenital hemolytic anemia
due to a new G-6-PD variant: G-6-PD Alhambra. Pediatrics 45: 230-235,
1970.

35. Beutler, E.; Westwood, B.; Prchal, J. T.; Vaca, G.; Bartsocas,
C. S.; Baronciani, L.: New glucose-6-phosphate dehydrogenase mutations
from various ethnic groups. Blood 80: 255-256, 1992.

36. Beutler, E.; Yoshida, A.: Human glucose-6-phosphate dehydrogenase
variants: a supplementary tabulation. Ann. Hum. Genet. 37: 151-156,
1973.

37. Boivin, P.; Galand, C.: Nouvelles variantes de la glucose-6-phosphate
dehydrogenase erythrocytaire. Rev. Franc. Etud. Clin. Biol. 13:
30-39, 1968.

38. Botha, M. C.; Dern, R. J.; Mitchell, M.; West, C.; Beutler, E.
: G6PD Capetown, a variant of glucose-6-phosphate dehydrogenase. Am.
J. Hum. Genet. 21: 547-551, 1969.

39. Boyer, S. H.; Graham, J. B.: Linkage between the X chromosome
loci for glucose-6-phosphate dehydrogenase electrophoretic variation
and hemophilia A. Am. J. Hum. Genet. 17: 320-324, 1965.

40. Boyer, S. H.; Porter, I. H.; Weilbaecher, R. G.: Electrophoretic
heterogeneity of glucose-6-phosphate dehydrogenase and its relationship
to enzyme deficiency in man. Proc. Nat. Acad. Sci. 48: 1868-1876,
1962.

41. Busch, D.; Bote, K.: Glucose-6-phosphate-dehydrogenase-Defect
in Deutschland. II. Bigenschabten des Enzyms (Typ Freiburg). Klin.
Wschr. 48: 74-78, 1970.

42. Calabro, V.; Giacobbe, A.; Vallone, D.; Montanaro, V.; Cascone,
A.; Filosa, S.; Battistuzzi, G.: Genetic heterogeneity at the glucose-6-phosphate
dehydrogenase locus in southern Italy: a study on a population from
the Matera district. Hum. Genet. 86: 49-53, 1990.

43. Calabro, V.; Mason, P. J.; Filosa, S.; Civitelli, D.; Cittadella,
R.; Tagarelli, A.; Martini, G.; Brancati, C.; Luzzatto, L.: Genetic
heterogeneity of glucose-6-phosphate dehydrogenase deficiency revealed
by single-strand conformation and sequence analysis. Am. J. Hum.
Genet. 52: 527-536, 1993.

44. Cappadoro, M.; Giribaldi, G.; O'Brien, E.; Turrini, F.; Mannu,
F.; Ulliers, D.; Simula, G.; Luzzatto, L.; Arese, P.: Early phagocytosis
of glucose-6-phosphate dehydrogenase (G6PD)-deficient erythrocytes
parasitized by Plasmodium falciparum may explain malaria protection
in G6PD deficiency. Blood 92: 2527-2534, 1998.

45. Cappellini, M. D.; Fiorelli, G.: Glucose-6-phosphate dehydrogenase
deficiency. Lancet 371: 64-74, 2008.

46. Cappellini, M. D.; Sampietro, M.; Toniolo, D.; Carandina, G.;
Pittalis, S.; Martinez di Montemuros, F.; Tavazzi, D.; Fiorelli, G.
: Biochemical and molecular characterization of a new sporadic glucose-6-phosphate
dehydrogenase variant described in Italy: G6PD Modena. Brit. J. Haemat. 87:
209-211, 1994.

47. Carandina, G.; Moretto, E.; Zecchi, G.; Conighi, C.: Glucose
6-phosphate dehydrogenase Ferrara. A new variant of G6PD identified
in Northern Italy. Acta Haemat. 56: 116-122, 1976.

48. Castro, A. M.; Snyder, L. M.: G6PD San Jose: a new variant characterized
by NADPH inhibition studies. Humangenetik 21: 361-363, 1974.

49. Cayanis, E.; Gomperts, E. D.; Balinsky, D.; Disler, P.; Myers,
A.: G6PD Hillbrow: a new variant of glucose-6-phosphate dehydrogenase
associated with drug-induced haemolytic anaemia. Brit. J. Haemat. 30:
343-350, 1975.

50. Cayanis, E.; Lane, A. B.; Jenkins, T.; Nurse, G. T.; Balinsky,
D.: Glucose-6-phosphate dehydrogenase Porbandar: a new slow variant
with slightly reduced activity in a South African family of Indian
descent. Biochem. Genet. 15: 765-773, 1977.

51. Cazzola, M.; Bergamaschi, G.: X-linked Wiskott-Aldrich syndrome
in a girl. (Letter) New Eng. J. Med. 338: 1850 only, 1998.

52. Cederbaum, A. I.; Beutler, E.: Nonspherocytic hemolytic anemia
due to G6PD Grand Prairie. I.R.C.S. 3: 579, 1975.

53. Chalvam, R.; Kedar, P. S.; Colah, R. B.; Ghosh, K.; Mukherjee,
M. B.: A novel R198H mutation in the glucose-6-phosphate dehydrogenase
gene in the tribal groups of the Nilgiris in southern India. J. Hum.
Genet. 53: 181-184, 2008.

54. Chalvam, R.; Mukherjee, M. B.; Colah, R. B.; Mohanty, D.; Ghosh,
K.: G6PD Namoru (208T-C) is the major polymorphic variant in the
tribal populations in southern India. (Letter) Brit. J. Haematol. 136:
512-513, 2006.

55. Chan, T. K.; Todd, D.: Characteristics and distribution of glucose-6-phosphate
dehydrogenase-deficient variants in South China. Am. J. Hum. Genet. 24:
475-484, 1972.

56. Chan, T. K.; Todd, D.; Lai, M. C. S.: Glucose 6-phosphate dehydrogenase:
identity of erythrocyte and leukocyte enzyme with report of a new
variant in Chinese. Biochem. Genet. 6: 119-124, 1972.

57. Chang, J.-G.; Chiou, S.-S.; Perng, L.-I.; Chen, T.-C.; Liu, T.-C.;
Lee, L.-S.; Chen, P.-H.; Tang, T. K.: Molecular characterization
of glucose-6-phosphate dehydrogenase (G6PD) deficiency by natural
and amplification created restriction sites: five mutations account
for most G6PD deficiency cases in Taiwan. Blood 80: 1079-1082, 1992.

58. Chen, E. Y.; Cheng, A.; Lee, A.; Kuang, W.-J.; Hillier, L.; Green,
P.; Schlessinger, D.; Ciccodicola, A.; D'Urso, M.: Sequence of human
glucose-6-phosphate dehydrogenase cloned in plasmids and a yeast artificial
chromosome. Genomics 10: 792-800, 1991.

59. Chen, H.-L.; Huang, M.-J.; Huang, C.-S.; Tang, T. K.: G6PD NanKang
(517 T-to-C; 173 phe-to-leu): a new Chinese G6PD variant associated
with neonatal jaundice. Hum. Hered. 46: 201-204, 1996.

60. Chernyak, N. B.; Batischev, A. I.; Lanzina, N. V.; Tokarev, Y.
N.; Alexeyev, G. A.: Electrophoretic and kinetic properties of glucose-6-phosphate
dehydrogenase from erythrocytes or patients with hemolytic anemia,
related to deficiency of the enzyme activity. Vopr. Med. Khim. 23:
166-171, 1977.

61. Childs, B.; Zinkham, W.; Browne, E. A.; Kimbro, E. L.; Torbert,
J. V.: A genetic study of a defect in glutathione metabolism of the
erythrocytes. Bull. Johns Hopkins Hosp. 102: 21-37, 1958.

62. Chiu, D. T. Y.; Zuo, L.; Chao, L.; Chen, E.; Louie, E.; Lubin,
B.; Liu, T. Z.; Du, C. S.: Molecular characterization of glucose-6-phosphate
dehydrogenase (G6PD) deficiency in patients of Chinese descent and
identification of new base substitutions in the human G6PD gene. Blood 81:
2150-2154, 1993.

63. Chockkalingam, K.; Board, P. G.: Further evidence for heterogeneity
of glucose-6-phosphate dehydrogenase deficiency in Papua New Guinea. Hum.
Genet. 56: 209-212, 1980.

64. Chockkalingam, K.; Board, P. G.; Breguet, G.: Glucose-6-phosphate
dehydrogenase variants of Bali Island (Indonesia). Hum. Genet. 60:
60-62, 1982.

65. Chockkalingam, K.; Board, P. G.; Nurse, G. T.: Glucose-6-phosphate
dehydrogenase deficiency in Papua New Guinea: the description of 13
new variants. Hum. Genet. 60: 189-192, 1982.

66. Chuanshu, D.; Yankang, X.; Lin, W. Q. R.; Xiaoyun, H.: Studies
on erythrocyte glucose-6-phosphate dehydrogenase variants in Chinese.
I. Gd(-) Lizu-Baisha. Acta Acad. Med. Zhong Shan 2: 649-658, 1981.

67. Cianfriglia, M.; Miggiano, V. C.; Meo, T.; Muller, H. J.; Muller,
E.; Battistuzzi, G.: Evidence for synteny between the rabbit gene
loci coding for HPRT, PGK and G6PD in mouse-rabbit somatic cell hybrids.
(Abstract) Cytogenet. Cell Genet. 25: 142, 1979.

68. Cohn, J.; Carter, N.; Warburg, M.: Glucose-6-phosphate dehydrogenase
deficiency in a native Danish family: a new variant. Scand. J. Haemat. 23:
403-406, 1979.

69. Colonna-Romano, S.; Iolascon, A.; Lippo, S.; Pinto, L.; Cutillo,
S.; Battistuzzi, G.: Genetic heterogeneity at the glucose-6-phosphate
dehydrogenase locus in southern Italy: a study on the population of
Naples. Hum. Genet. 69: 228-232, 1985.

70. Cooper, D. W.; Johnston, P. G.; Murtagh, C. E.; Sharman, G. B.;
Vandeberg, J. L.; Poole, W. E.: Sex-linked isozymes and sex-chromosome
evolution and inactivation in kangaroos.In: Markeit, C. L.: Isozymes.
Developmental Biology. New York: Academic Press (pub.) III: 1975.
Pp. 559-573.

71. Corash, L.; Spielberg, S.; Bartsocas, C.; Boxer, L.; Steinherz,
R.; Sheetz, M.; Egan, M.; Schlessleman, J.; Schulman, J. D.: Reduced
chronic hemolysis during high-dose vitamin E administration in Mediterranean-type
glucose-6-phosphate dehydrogenase deficiency. New Eng. J. Med. 303:
416-420, 1980.

72. Corcoran, C. M.; Calabro, V.; Tamagnini, G.; Town, M.; Haidar,
B.; Vulliamy, T. J.; Mason, P. J.; Luzzatto, L.: Molecular heterogeneity
underlying the G6PD Mediterranean phenotype. Hum. Genet. 88: 688-690,
1992.

73. Costa, E.; Cabeda, J. M.; Vieira, E.; Pinto, R.; Pereira, S. A.;
Ferraz, L.; Santos, R.; Barbot, J.: Glucose-6-phosphate dehydrogenase
Aveiro: a de novo mutation associated with chronic nonspherocytic
hemolytic anemia. Blood 95: 1499-1501, 2000.

74. Crookston, J. H.; Yoshida, A.; Lin, M.; Booser, D. J.: G6PD Toronto. Biochem.
Genet. 8: 259-265, 1973.

75. Csepreghy, M.; Hall, M. K.; Berkow, R. L.; Jackson, S.; Prchal,
J. T.: Characterization of a new G6PD variant: G6PD Titusville. Am.
J. Med. Sci. 297: 114-117, 1989.

76. Csepreghy, M.; Yeilding, A.; Lilly, M.; Hall, K.; Scott, C. W.;
Prchal, J. T.: Characterization of a new glucose-6-phosphate dehydrogenase
variant: G6PD Central City. Am. J. Hemat. 28: 61-62, 1988.

77. D'Urso, M.; Luzzatto, L.; Perroni, L.; Ciccodicola, A.; Gentile,
G.; Peluso, I.; Persico, M. G.; Pizzella, T.; Toniolo, D.; Vulliamy,
T. J.: An extensive search for RFLP in the human glucose-6-phosphate
dehydrogenase locus has revealed a silent mutation in the coding sequence. Am.
J. Hum. Genet. 42: 735-741, 1988.

78. Davidson, R. G.; Nitowsky, H. M.; Childs, B.: Demonstration of
two populations of cells in the human female heterozygous for glucose-6-phosphate
dehydrogenase variants. Proc. Nat. Acad. Sci. 50: 481-485, 1963.

79. De Flora, A.; Morelli, A.; Benatti, U.; Giuntini, P.; Ferraris,
A. M.; Galiano, S.; Ravazzolo, R.; Gaetani, G. F.: G6PD Napoli and
Ferrara II: two new glucose-6-phosphate dehydrogenase variants having
similar characteristics but different intracellular lability and specific
activity. Brit. J. Haemat. 48: 417-423, 1981.

80. Dern, R. J.; McCurdy, P. R.; Yoshida, A.: A new structural variant
of glucose-6-phosphate dehydrogenase with a high production rate (G6PD
Hektoen). J. Lab. Clin. Med. 73: 283-290, 1969.

81. De Vita, G.; Alcalay, M.; Sampietro, M.; Cappelini, M. D.; Fiorelli,
G.; Toniolo, D.: Two point mutations are responsible for G6PD polymorphism
in Sardinia. Am. J. Hum. Genet. 44: 233-240, 1989.

82. Du, C.; Xu, Y.; Hua, X.; Wu, Q.; Liu, L.; Wu, M.: Studies on
erythrocyte glucose-6-phosphate dehydrogenase variants in Chinese.
III: Gd(-) Miaozu-Baisha. Acta Genet. Sin. 11(2): 153-158, 1984.

83. Du, C.-S.; Hua, X.-Y.; Wu, Q.-L.; Li, C.-Q.; Zheng, J.-F.; Li,
H.-L.: Studies on erythrocyte glucose-6-phosphate dehydrogenase variants
in Chinese. IV. Gd(-) Gaohe associated with paroxysmal nocturnal hemoglobinuria. Chinese
J. Pathophysiol. 1: 12-15, 1985.

84. Du, C. S.; Xu, Y. K.; Hua, X. Y.; Wu, Q. L.; Liu, L. B.: Glucose-6-phosphate
dehydrogenase variants and their frequency in Guangdong, China. Hum.
Genet. 80: 385-388, 1988.

85. Eber, S. W.; Gahr, M.; Schroter, W.: Glucose-6-phosphate dehydrogenase
(G6PD) Iserlohn and G6PD Regensburg: two new severe enzyme defects
in German families. Blut 51: 109-115, 1985.

86. Echard, G.; Gillois, M.: G6PD--alpha-GAL-PGK--HPRT synteny in
the rabbit, Oryctolagus cunniculus. (Abstract) Cytogenet. Cell Genet. 25:
148-149, 1979.

87. Efferth, T.; Bachli, E. B.; Schwarzl, S. M.; Goede, J. S.; West,
C.; Smith, J. C.; Beutler, E.: Glucose-6-phosphate dehydrogenase
(G6PD) deficiency-type Zurich: a splice site mutation as an uncommon
mechanism producing enzyme deficiency. (Letter) Blood 15: 2608 only,
2004.

88. Elizondo, J.; Saenz, G. F.; Paez, C. A.; Ramon, M.; Garcia, M.;
Gutierrez, A.; Estrada, M.: G6PD Puerto Limon: a new deficient variant
of glucose-6-phosphate dehydrogenase associated with congenital nonspherocytic
hemolytic anemia. Hum. Genet. 62: 110-112, 1982.

89. Engstrom, P. F.; Beutler, E.: G-6-PD Tripler: a unique variant
associated with chronic hemolytic disease. Blood 36: 10-13, 1970.

90. Epstein, C. J.: Mammalian oocytes: X-chromosome activity. Science 163:
1078-1079, 1969.

91. Ermakov, N. V.; Chernyak, N. B.; Tokarev, Y. N.: Properties of
new variant of glucose-6-phosphate dehydrogenase (Regar variant):
glucose metabolism in erythrocytes containing abnormal enzyme. Biokhimiia 48:
577-583, 1983.

92. Estrada, M.; Garcia, M.; Gutierrez, A.; Quintero, I.; Gonzalez,
R.: G6PD Varadero. Vox Sang. 43: 102-104, 1982.

93. Fairbanks, V. F.; Nepo, A. G.; Beutler, E.; Dickson, E. R.; Honig,
G.: Glucose-6-phosphate dehydrogenase variants: reexamination of
G6PD Chicago and Cornell and a new variant (G6PD Pea Ridge) resembling
G6PD Chicago. Blood 55: 216-220, 1980.

94. Faust, C. J.; Levinson, B.; Gitschier, J.; Herman, G. E.: Extension
of the physical map in the region of the mouse X chromosome homologous
to human Xq28 and identification of an exception to conserved linkage. Genomics 13:
1289-1295, 1992.

95. Feldman, R.; Gromisch, D. S.; Luhby, A. L.; Beutler, E.: Congenital
nonspherocytic hemolytic anemia due to glucose-6-phosphate dehydrogenase
East Harlem: a new deficient variant. J. Pediat. 90: 89-91, 1977.

96. Fernandez, M.; Fairbanks, V. F.: Glucose-6-phosphate dehydrogenase
deficiency in the Philippines: report of a new variant--G6PD Panay. Mayo
Clin. Proc. 43: 645-660, 1968.

97. Filosa, E.: Personal Communication. La Jolla, Calif. 1989.

98. Filosa, S.; Calabro, V.; Vallone, D.; Poggi, V.; Mason, P.; Pagnini,
D.; Alfinito, F.; Rotoli, B.; Martini, G.; Luzzatto, L.; Battistuzzi,
G.: Molecular basis of chronic non-spherocytic haemolytic anaemia:
a new G6PD variant (393arg-to-his) with abnormal K(m) G6P and marked
in vivo instability. Brit. J. Haemat. 80: 111-116, 1992.

99. Filosa, S.; Giacometti, N.; Wangwei, C.; De Mattia, D.; Pagnini,
D.; Alfinito, F.; Schettini, F.; Luzzatto, L.; Martini, G.: Somatic-cell
selection is a major determinant of the blood-cell phenotype in heterozygotes
for glucose-6-phosphate dehydrogenase mutations causing severe enzyme
deficiency. Am. J. Hum. Genet. 59: 887-895, 1996.

100. Fiorelli, G.; Manoussakis, C.; Sampietro, M.; Pittalis, S.; Guglielmino,
C. R.; Cappellini, M. D.: Different polymorphic variants of glucose-6-phosphate
dehydrogenase (G6PD) in Italy. Ann. Hum. Genet. 53: 229-236, 1989.

101. Fite, E.; Morell, F.; Zuazu, J.; Julia, A.; Morera, J.: Leucocyte
glucose-6-phosphate dehydrogenase deficiency and necrotizing pneumonia. Europ.
J. Resp. Dis. 64: 150-154, 1983.

102. Francke, U.; Bakay, B.; Connor, J. D.; Coldwell, J. G.; Nyhan,
W. L.: Linkage relationships of X-linked enzymes glucose-6-phosphate
dehydrogenase and hypoxanthine guanine phosphoribosyltransferase. Am.
J. Hum. Genet. 26: 512-522, 1974.

103. Friedman, M. J.; Trager, W.: The biochemistry of resistance
to malaria. Sci. Am. 244(3): 154-164, 1981.

104. Frigerio, R.; Sole, G.; Olla, N.; Lovicu, M.; Passiu, G.; Carcassi,
U.: Cagliari II: a new G-6-PD variant. Haematologica 72: 241-243,
1987.

105. Fujii, H.; Miwa, S.; Takegawa, S.; Takahashi, K.; Hirono, A.;
Takizawa, T.; Morisaki, T.; Kanno, H.; Taguchi, T.; Okamura, J.:
Gd(-) Gifu and Gd(-) Fukuoka: two new variants of glucose-6-phosphate
dehydrogenase found in Japan. Hum. Genet. 66: 276-278, 1984.

106. Fujii, H.; Miwa, S.; Tani, K.; Takegawa, S.; Fujinami, N.; Takahashi,
K.; Nakayama, S.; Konno, M.; Sato, T.: Glucose 6-phosphate dehydrogenase
variants: a unique variant (G6PD Kobe) showed an extremely increased
affinity for galactose 6-phosphate and a new variant (G6PD Sapporo)
resembling G6PD Pea Ridge. Hum. Genet. 58: 405-407, 1981.

107. Fusco, F.; Paciolla, M.; Napolitano, F.; Pescatore, A.; D'Addario,
I.; Bal, E.; Lioi, M. B.; Smahl, A.; Miano, M. G.; Ursini, M. V.:
Genomic architecture at the incontinentia pigmenti locus favours de
novo pathological alleles through different mechanisms. Hum. Molec.
Genet. 21: 1260-1271, 2012.

108. Gaetani, G. F.; Galiano, S.; Melani, C.; Miglino, M.; Forni,
G. L.; Napoli, G.; Perrone, L.; Ferraris, A. M.: A new glucose-6-phosphate
dehydrogenase variant with congenital nonspherocytic hemolytic anemia
(G6PD Genova): biochemical characterization and mosaicism expression
in the heterozygote. Hum. Genet. 84: 337-340, 1990.

109. Gahr, M.; Bornhalm, D.; Schroeter, W.: Biochemische Eigenschaften
einer neuen Variante des Glucose-6-phosphadehydrogenase (G6PD) Mangels
mit Favismus: G6PD Bielefeld. Klin. Wschr. 55: 379-384, 1977.

110. Gahr, M.; Bornhalm, D.; Schroeter, W.: Haemolytic anemia due
to glucose 6-phosphate dehydrogenase (G6PD) deficiency: demonstration
of two new biochemical variants, G6PD Hamm and G6PD Tarsus. Brit.
J. Haemat. 33: 363-370, 1976.

111. Gahr, M.; Schroeter, W.: Glucose 6-phosphate dehydrogenase (G6PD)
Hamburg, a new variant with chronic nonspherocytic hemolytic anemia. Europ.
J. Clin. Invest. 4: 187-191, 1974.

112. Gahr, M.; Schroeter, W.; Sturzenegger, M.; Bornhalm, D.; Marti,
H. R.: Glucose 6-phosphate dehydrogenase (G6PD) deficiency in Switzerland. Helv.
Paediat. Acta 31: 159-166, 1976.

113. Geerdink, R. A.; Horst, R.; Staal, G. E.: An Iraqi Jewish family
with a new red cell glucose 6-phosphate dehydrogenase variant (Gd-Bagdad)
and kernicterus. Isr. J. Med. Sci. 9: 1040-1043, 1973.

114. Gellin, J.; Benne, F.; Renard, C.; Vaiman, M.; Hors-Cayla, M.
C.; Gillois, M.: Pig gene mapping: synteny, attempt to assign the
histocompatibility complex (SLA). (Abstract) Cytogenet. Cell Genet. 25:
159, 1979.

115. Gomez-Gallego, F.; Garrido-Pertierra, A.; Bautista, J. M.: Structural
defects underlying protein dysfunction in human glucose-6-phosphate
dehydrogenase A- deficiency. J. Biol. Chem. 275: 9256-9262, 2000.

116. Gonzalez, R.; Estrada, M.; Garcia, M.; Gutierrez, A.: G6PD Ciudad
de la Habana: a new slow variant with deficiency found in a Cuban
family. Hum. Genet. 55: 133-135, 1980.

117. Gonzalez, R.; Wade, M.; Estrada, M.; Svarch, E.; Colombo, B.
: G6PD Pinar del Rio: a new variant discovered in a Cuban family. Biochem.
Genet. 15: 909-913, 1977.

118. Goss, S. J.; Harris, H.: Gene transfer by means of cell fusion.
I. Statistical mapping of the human X-chromosome by analysis of radiation
induced gene segregation. J. Cell Sci. 25: 17-37, 1977.

119. Gourdin, D.; Vergnes, H.; Bouloux, C.; Ruffie, J.; Gherardi,
M.: Polymorphism of erythrocyte G6PD in the baboon. Am. J. Phys.
Anthrop. 37: 281-288, 1972.

120. Gray, G. R.; Stamatoyannopoulos, G.; Naiman, S. C.; Kliman, M.
R.; Klebanoff, S. J.; Austin, T.; Yoshida, A.; Robinson, G. C. G.
: Neutrophil dysfunction, chronic granulomatous disease, and non-spherocytic
haemolytic anaemia caused by complete deficiency of glucose-6-phosphate
dehydrogenase. Lancet 302: 530-534, 1973. Note: Originally Volume
II.

121. Grossman, A.; Ramanathan, K.; Justice, P.; Gordon, J.; Shahidi,
N. T.; Hsia, D. Y. Y.: Congenital nonspherocytic hemolytic anemia
associated with erythrocyte G-6-PD deficiency in a Negro family. Pediatrics 37:
624-629, 1966.

122. Gutierrez, A.; Garcia, M.; Estrada, M.; Quintero, I.; Gonzalez,
R.: Glucose-6-phosphate dehydrogenase (G6PD) Guantanamo and G6PD
Caujeri: two new glucose-6-phosphate dehydrogenase-deficient variants
found in Cuba. Biochem. Genet. 25: 231-238, 1987.

123. Hall, K.; Schreeder, M. T.; Prchal, J. T.: G6PD Huntsville:
a new glucose-6-phosphate dehydrogenase associated with chronic hemolytic
anemia. Hum. Genet. 79: 90-91, 1988.

124. Harkonen, M.; Vuopio, P.: Red cell glucose-6-phosphate dehydrogenase
deficiency in Finland. Ann. Clin. Res. 6: 187-197, 1974.

125. Harley, J. D.; Agar, N. S.; Yoshida, A.: Glucose 6-phosphate
dehydrogenase variant Gd(+) Alexandra associated with neonatal jaundice
and Gd(-) Camperdown in a young man with lamellar cataracts. J. Lab.
Clin. Med. 91: 295-300, 1978.

126. Helge, H.; Borner, K.: Kongenitale nichtsphaerozytare haemolytische
Anaemie, Katarakt und Glucose-6-phosphat-dehydrogenase-mangel. Dtsch.
Med. Wschr. 91: 1584-1589, 1966.

127. Hirono, A.; Beutler, E.: Alternative splicing of human glucose-6-phosphate
dehydrogenase messenger RNA in different tissues. J. Clin. Invest. 83:
343-346, 1989.

128. Hirono, A.; Beutler, E.: Molecular cloning and nucleotide sequence
of cDNA for human glucose-6-phosphate dehydrogenase variant A(-). Proc.
Nat. Acad. Sci. 85: 3951-3954, 1988.

129. Hirono, A.; Fujii, H.; Shima, M.; Miwa, S.: G6PD Nara: a new
class 1 glucose-6-phosphate dehydrogenase variant with an eight amino
acid deletion. Blood 82: 3250-3252, 1998.

130. Hirono, A.; Kawate, K.; Honda, A.; Fujii, H.; Miwa, S.: A single
mutation 202G-A in the human glucose-6-phosphate dehydrogenase gene
(G6PD) can cause acute hemolysis by itself. (Letter) Blood 99: 1498
only, 2002.

131. Hirono, A.; Kuhl, W.; Gelbart, T.; Forman, L.; Fairbanks, V.
F.; Beutler, E.: Identification of the binding domain for NADP(+)
of human glucose-6-phosphate dehydrogenase by sequence analysis of
mutants. Proc. Nat. Acad. Sci. 86: 10015-10017, 1989.

132. Hitzeroth, H. W.; Bender, K.: Age-dependency of somatic selection
in South African Negro G-6-PD heterozygotes. Hum. Genet. 58: 338-343,
1981.

133. Honig, G. R.; Habacon, E.; Vida, L. N.; Matsumoto, F.; Beutler,
E.: Three new variants of glucose-6-phosphate dehydrogenase associated
with chronic nonspherocytic hemolytic anemia: G6PD Lincoln Park, G6PD
Arlington Heights, and G6PD West Town. Am. J. Hemat. 6: 353-360,
1979.

134. Hook, E. B.; Stamatoyannopoulos, G.; Yoshida, A.; Motulsky, A.
G.: Glucose-6-phosphate dehydrogenase Madrona: a slow electrophoretic
glucose-6-phosphate dehydrogenase variant with kinetic characteristics
similar to those of normal type. J. Lab. Clin. Med. 72: 404-409,
1968.

135. Hors-Cayla, M. C.; Heuertz, S.; Van Cong, N.; Benne, F.: Cattle
gene mapping by somatic cell hybridization. (Abstract) Cytogenet.
Cell Genet. 25: 165-166, 1979.

136. Howell, E. B.; Nelson, A. J.; Jones, O. W.: A new G-6-PD variant
associated with chronic non-spherocytic haemolytic anaemia in a Negro
family. J. Med. Genet. 9: 160-164, 1972.

137. Hutz, M. H.; Yoshida, A.; Salzano, F. M.: Three rare G-6-PD
variants from Porto Alegre, Brazil. Hum. Genet. 39: 191-197, 1977.

138. Iancovici-Kidon, M.; Sthoeger, D.; Abrahamov, A.; Wolach, B.;
Beutler, E.; Gelbart, T.; Barak, Y.: A new exon 9 glucose-6-phosphate
dehydrogenase mutation (G6PD 'Rehovot') in a Jewish Ethiopian family
with variable phenotypes. Blood Cells Molec. Dis. 26: 567-571, 2000.
Note: Erratum: Blood Cells Molec. Dis. 27: 351 only, 2001.

139. Ishwad, C. S.; Naik, S. N.: A new glucose-6-phosphate dehydrogenase
variant (G-6-PD Kalyan) found in a Koli family. Hum. Genet. 66:
171-175, 1984.

140. Iwai, K.; Hirono, A.; Matsuoka, H.; Kawamoto, F.; Horie, T.;
Lin, K.; Tantular, I. S.; Dachlan, Y. P.; Notopuro, H.; Hidayah, N.
I.; Salim, A. M. A.; Fujii, H.; Miwa, S.; Ishii, A.: Distribution
of glucose-6-phosphate dehydrogenase mutations in Southeast Asia. Hum.
Genet. 108: 445-449, 2001.

141. Jain, M.; Cui, L.; Brenner, D. A.; Wang, B.; Handy, D. E.; Leopold,
J. A.; Loscalzo, J.; Apstein, C. S.; Liao, R.: Increased myocardial
dysfunction after ischemia-reperfusion in mice lacking glucose-6-phosphate
dehydrogenase. Circulation 109: 898-903, 2004.

142. Jiang, W.; Yu, G.; Liu, P.; Geng, Q.; Chen, L.; Lin, Q.; Ren,
X.; Ye, W.; He, Y.; Guo, Y.; Duan, S.; Wen, J.; and 9 others: Structure
and function of glucose-6-phosphate dehydrogenase-deficient variants
in Chinese population. Hum. Genet. 119: 463-478, 2006.

143. Johnson, G. J.; Kaplan, M. E.; Beutler, E.: G6PD Long Prairie:
a new mutant exhibiting normal sensitivity to inhibition by NADPH
and accompanied by nonspherocytic hemolytic anemia. Blood 49: 247-251,
1977.

144. Johnston, P. G.; VandeBerg, J. L.; Sharman, G. B.: Inheritance
of erythrocyte glucose 6-phosphate dehydrogenase in the red-necked
wallaby, Macropus rufogriseus (Desmarest) consistent with paternal
X inactivation. Biochem. Genet. 13: 235-242, 1975.

145. Junien, C.; Kaplan, J.-C.; Meienhofer, M. C.; Maigret, P.; Sender,
A.: G6PD Baudelocque: a new unstable variant characterized in cultured
fibroblasts. Enzyme 18: 48-59, 1974.

146. Kaeda, J. S.; Chhotray, G. P.; Ranjit, M. R.; Bautista, J. M.;
Reddy, P. H.; Stevens, D.; Naidu, J. M.; Britt, R. P.; Vulliamy, T.
J.; Luzzatto, L.; Mason, P. J.: A new glucose-6-phosphate dehydrogenase
variant, G6PD Orissa (44 ala-gly), is the major polymorphic variant
in tribal populations in India. Am. J. Hum. Genet. 57: 1335-1341,
1995.

147. Kageoka, T.; Satoh, C.; Goriki, K.; Fujita, M.; Neriishi, S.;
Yamamura, K.; Kaneko, J.; Masunari, N.: Electrophoretic variants
of blood proteins in Japanese. IV. Prevalence and enzymologic characteristics
of G6PD variants in Hiroshima and Nagasaki. Hum. Genet. 70: 101-108,
1985.

148. Kahn, A.; Bernard, J.-F.; Cottreau, D.; Mazie, J.; Boivin, P.
: Gd(-) Abrami, a deficient G6PD variant with hemizygous expression
in blood cells of a woman with primary myelofibrosis. Humangenetik 30:
41-46, 1975.

149. Kahn, A.; Boivin, P.; Hakim, J.; Lagneau, J.: Heterogeneite
des glucose-6-phosphate dehydrogenase erythrocytaire deficitaires
dans la race noire: etude cinetique et description de deux nouvelles
variants Gd(-) Dakar et Gd(-) Mali. Nouv. Rev. Franc. Hemat. 11:
741-758, 1971.

150. Kahn, A.; Boivin, P.; Lagneau, J.: Phenotypes de la glucose-6-phosphate
dehydrogenase erythrocytaire dans la race noire. Humangenetik 18:
261-270, 1973.

151. Kahn, A.; Boulard, M.; Hakim, J.; Schaison, G.; Boivin, P.; Bernard,
J.: Anemie hemolytique congenitale non spherocytaire par deficit
en glucose 6-phosphate dehydrogenase erythrocytaire: description de
deux nouvelles variants: Gd(-) Saint Louis (Paris) et Gd(-) Hayem. Nouv.
Rev. Franc. Hemat. 14: 587-600, 1974.

152. Kahn, A.; Dao, C.; Cottreau, D.; Bilski-Pasquier, G.: 'Gd(-)
Hotel Dieu': a new G-6PD variant with chronic hemolysis in a Negro
patient from Senegal. Hum. Genet. 39: 353-358, 1977.

153. Kahn, A.; Exters, A.; Habedank, M.: Gd(-) Aachen, a new variant
of deficient glucose-6-phosphate dehydrogenase. Humangenetik 32:
171-180, 1976.

154. Kahn, A.; Hakim, J.; Cottreau, D.; Boivin, P.: Gd (-) Matam.
An African glucose 6-phosphate dehydrogenase variant with enzyme deficiency.
Biochemical and immunological properties in various hemopoietic tissues. Clin.
Chim. Acta 59: 183-190, 1975.

155. Kahn, A.; North, M. L.; Cottreau, D.; Giron, G.; Lang, J. M.
: G6PD Vientiane: a new glucose-6-phosphate dehydrogenase variant
with increased stability. Hum. Genet. 43: 85-89, 1978.

156. Kahn, A.; North, M. L.; Messer, J.; Boivin, P.: G-6PD 'Ankara':
a new G-6PD variant with deficiency found in a Turkish family. Humangenetik 27:
247-250, 1975.

157. Kanno, H.; Huang, I.-Y.; Kan, Y. W.; Yoshida, A.: Two structural
genes on different chromosomes are required for encoding the major
subunit of human red cell glucose-6-phosphate dehydrogenase. Cell 58:
595-606, 1989.

158. Kanno, H.; Takano, T.; Fujii, H.; Tani, K.; Morisaki, T.; Hirono,
A.; Kumakawa, T.; Ogura, H.; Takahashi, K.; Tsutsumi, H.; Miwa, S.
: A new glucose-6-phosphate variant (G6PD Iwate) associated with congenital
non-spherocytic hemolytic anemia. Acta Haemat. Jpn. 51: 715-719,
1987.

159. Kaplan, J. C.; Hanzlickova-Leroux, A.; Nicholas, A. M.; Rosa,
R.; Weiler, C.; Lepercq, G.: A new glucose-6-phosphate dehydrogenase
variant (G6PD Port-Royal). Enzyme 12: 25-32, 1971.

160. Kaplan, J. C.; Rosa, R.; Seringe, P.; Hoeffel, J. C.: Le polymorphisme
genetique de la glucose-6-phosphate deshydrogenase erythrocytaire
chez l'homme. II. Etude d'une nouvelle variete a activite diminuee:
le type 'Kabyle.'. Enzym. Biol. Clin. 8: 332-340, 1967.

161. Kaplan, M.; Hammerman, C.; Vreman, H. J.; Stevenson, D. K.; Beutler,
E.: Acute hemolysis and severe neonatal hyperbilirubinemia in glucose-6-phosphate
dehydrogenase deficient heterozygotes. J. Pediat. 139: 137-140,
2001.

162. Kaplan, M.; Renbaum, P.; Levy-Lahad, E.; Hammerman, C.; Lahad,
A.; Beutler, E.: Gilbert syndrome and glucose-6-phosphate dehydrogenase
deficiency: a dose-dependent genetic interaction crucial to neonatal
hyperbilirubinemia. Proc. Nat. Acad. Sci. 94: 12128-12132, 1997.

163. Karadsheh, N. S.; Awidi, A. S.; Tarawneh, M. S.: Two new glucose-6
phosphate dehydrogenase (G6PD) variants associated with hemolytic
anemia: G6PD Amman-1 and G6PD Amman-2. Am. J. Hemat. 22: 185-192,
1986.

164. Kay, A. C.; Kuhl, W.; Prchal, J.; Beutler, E.: The origin of
glucose-6-phosphate-dehydrogenase (G6PD) polymorphisms in African-Americans. Am.
J. Hum. Genet. 50: 394-398, 1992.

165. Kirkman, H. N.; Kidson, C.; Kennedy, M.: Variants of human glucose-6-phosphate
dehydrogenase. Studies of samples from New Guinea.In: Beutler, E.
: Hereditary Disorders of Erythrocyte Metabolism. New York: Grune
and Stratton (pub.) 1968. Pp. 126-145.

166. Kirkman, H. N.; Lie-Injo, L. E.: Variants of glucose 6-phosphate
dehydrogenase in Indonesia. Nature 221: 959, 1969.

167. Kirkman, H. N.; McCurdy, P. R.; Naiman, J. L.: Functionally
abnormal glucose-6-phosphate dehydrogenases. Cold Spring Harbor Symp.
Quant. Biol. 29: 391-398, 1964.

168. Kirkman, H. N.; Ramot, B.; Lee, J. T.: Altered aggregational
properties in a genetic variant of human glucose-6-phosphate dehydrogenase. Biochem.
Genet. 3: 137-150, 1969.

169. Kirkman, H. N.; Riley, H. D., Jr.: Congenital nonspherocytic
hemolytic anemia. Am. J. Dis. Child. 102: 313-320, 1961.

170. Kirkman, H. N.; Rosenthal, I. M.; Simon, E. B.; Carson, P. E.;
Brinson, A. G.: 'Chicago I' variant of glucose-6-phosphate dehydrogenase
in congenital hemolytic disease. J. Lab. Clin. Med. 63: 715-725,
1964.

171. Kirkman, H. N.; Schettini, E.; Pickard, B. M.: Mediterranean
variant of glucose-6-phosphate dehydrogenase. J. Lab. Clin. Med. 63:
726-735, 1964.

172. Kirkman, H. N.; Simon, E. R.; Pickard, B. M.: Seattle variant
of glucose-6-phosphate dehydrogenase. J. Lab. Clin. Med. 66: 834-840,
1965.

173. Kissin, C.; Cotte, J.: Etude d'un variant de glucose-6-phosphate
deshydrogenase: I B type Constantine. Enzyme 11: 277-284, 1970.

174. Kitao, T.; Ito, K.; Hattori, K.; Matsuki, T.; Yoneyama, Y.:
G6PD Kanazawa: a new variant of glucose-6-phosphate dehydrogenase
associated with congenital nonspherocytic hemolytic anemia. Acta
Haemat. 68: 131-135, 1982.

175. Kojima, H.: Congenital nonspherocytic hemolytic disease (CNHD)
due to a G-6-PD variant: G-6-PD Kyoto. Acta Haemat. Jpn. 35: 32-38,
1972.

176. Koliakos, G.; Kalomenopoulou, M.; Grammatikos, P.; Dimitriadou,
A.; Kouzi-Koliakos, K.; Zacharaki, R.; Skaragas, G.; Kokka, A.; Trakatellis,
A.: A new glucose 6-phosphate dehydrogenase variant (G6PD Thessaloniki)
in a patient with idiopathic myelofibrosis. Hum. Hered. 39: 141-149,
1989.

177. Krasnopolskaya, K. D.; Bochkov, N. P.: Genetic heterogeneity
of hereditary enzymopathies. Vestn. Akad. Med. Nauk. SSSR 9: 56-64,
1982.

178. Krasnopolskaya, K. D.; Shatskaya, T. L.; Filippov, I. K.; Annenkov,
G. A.; Zakharova, T. V.; Mekhtiev, N. K.; Movsum-Zade, K. M.: Genetic
heterogeneity of G6PD deficiency: study of mutant alleles in Shekii
district of Azerbaijan. Genetika 13: 1455-1461, 1977.

179. Kumakawa, T.; Suzuki, S.; Fujii, H.; Miwa, S.: Frequency of
glucose 6-phosphate dehydrogenase (G6PD) deficiency in Tokyo and a
new variant: G6PD Musashino. Acta Haemat. Jpn. 50: 25-28, 1987.

180. Kurdi-Haidar, B.; Mason, P. J.; Berrebi, A.; Ankra-Badu, G.;
Al-Ali, A.; Oppenheim, A.; Luzzatto, L.: Origin and spread of the
glucose-6-phosphate dehydrogenase variant (G6PD-Mediterranean) in
the Middle East. Am. J. Hum. Genet. 47: 1013-1019, 1990.

181. Kwiatkowska, J.; Kacprzak-Bergman, I.: New erythrocyte glucose
6-phosphate dehydrogenase variant. Acta Haemat. 46: 188-192, 1971.

182. Kwok, C. J.; Martin, A. C. R.; Au, S. W. N.; Lam, V. M. S.:
G6PDdb, an integrated database of glucose-6-phosphate dehydrogenase
(G6PD) mutations. Hum. Mutat. 19: 217-224, 2002.

183. Lenzerini, L.; Meera Khan, P.; Filippi, G.; Rattazzi, M. C.;
Rat, A. K.: Characterization of glucose-6-phosphate dehydrogenase
variants. I. Occurrence of a G6PD Seattle-like variant in Sardinia
and its interaction with G6PD Mediterranean variant. Am. J. Hum.
Genet. 21: 142-153, 1969.

184. Leopold, J. A.; Dam, A.; Maron, B. A.; Scribner, A. W.; Liao,
R.; Handy, D. E.; Stanton, R. C.; Pitt, B.; Loscalzo, J.: Aldosterone
impairs vascular reactivity by decreasing glucose-6-phosphate dehydrogenase
activity. Nature Med. 13: 189-197, 2007. Note: Erratum: Nature Med.
15: 1093 only, 2009.

185. Lisker, R.; Linares, C.; Motulsky, A. G.: Glucose-6-phosphate
dehydrogenase Mexico, a new variant with enzyme deficiency, abnormal
mobility and absence of hemolysis. J. Lab. Clin. Med. 29: 788-793,
1972.

186. Lisker, R.; Perez-Briceno, R.; Beutler, E.: A new glucose-6-phosphate
dehydrogenase variant, Gd(-) Tepic, characterized by moderate enzyme
deficiency and mild episodes of hemolytic anemia. Hum. Genet. 69:
19-21, 1985.

187. Lisker, R.; Perez-Briceno, R.; Rave, V.; Yoshida, A.: Glucosa-6-fosfato
deshidrogenasa Gd(-) Distrito Federal: nueva variante asociada a deficiencia
enzimatica moderada y anemia hemolitica ocasional. Rev. Invest. Clin. 33:
209-211, 1981.

188. Lisker, R.; Perez Briceno, R.; Agrilar, L.; Yoshida, A.: A variant
glucose-6-phosphate dehydrogenase Gd(-) Chiapas associated with moderate
enzyme deficiency and occasional hemolytic anemia. Hum. Genet. 43:
81-84, 1978.

189. Lisker, R.; Perez Briceno, R.; Zavala, C.; Navarrette, J. I.;
Wessels, M.; Yoshida, A.: A glucose 6-phosphate dehydrogenase Gd(-)
Castilla variant characterized by mild deficiency associated with
drug-induced hemolytic anemia. J. Lab. Clin. Med. 90: 754-759, 1977.

190. Liu, Y.; Phelan, J.; Go, R. C. P.; Prchal, J. F.; Prchal, J.
T.: Rapid determination of clonality by detection of two closely-linked
X chromosome exonic polymorphisms using allele-specific PCR. J. Clin.
Invest. 99: 1984-1990, 1997.

191. Long, W. K.; Kirkman, H. N.; Sutton, H. H.: Electrophoretically
slow variants of glucose-6-phosphate dehydrogenase from red cells
of Negroes. J. Lab. Clin. Med. 65: 81-87, 1965.

192. Longo, L.; Vanegas, O. C.; Patel, M.; Rosti, V.; Li, H.; Waka,
J.; Merghoub, T.; Pandolfi, P. P.; Notaro, R.; Manova, K.; Luzzatto,
L.: Maternally transmitted severe glucose 6-phosphate dehydrogenase
deficiency is an embryonic lethal. EMBO J. 21: 4229-4239, 2002.

193. Louicharoen, C.; Nuchprayoon, I.: G6PD Viangchan (871G-A) is
the most common G6PD-deficient variant in the Cambodian population. J.
Hum. Genet. 50: 448-452, 2005.

194. Louicharoen, C.; Patin, E.; Paul, R.; Nuchprayoon, I.; Witoonpanich,
B.; Peerapittayamongkol, C.; Casademont, I.; Sura, T.; Laird, N. M.;
Singhasivanon, P.; Quintana-Murci, L.; Sakuntabhai, A.: Positively
selected G6PD-Mahidol mutation reduces Plasmodium vivax density in
Southeast Asians. Science 326: 1546-1549, 2009.

195. Luzzatto, L.: Personal Communication. London, England 4/1990.

196. Luzzatto, L.: Genetic heterogeneity and pathophysiology of G6PD
deficiency. Brit. J. Haemat. 28: 151-156, 1974.

197. Luzzatto, L.; Afolayam, A.: Enzyme properties of different types
of human erythrocyte glucose-6-phosphate dehydrogenase with characterization
of two new genetic variants. J. Clin. Invest. 47: 1833-1842, 1968.

198. Luzzatto, L.; Usanga, E. A.; Bienzle, U.; Esan, G. F. J.; Fusuan,
F. A.: Imbalance in X-chromosome expression: evidence for a human
X-linked gene affecting growth of hemopoietic cells. Science 205:
1418-1420, 1979.

199. Luzzatto, L.; Usanga, E. A.; Reddy, S.: Glucose-6-phosphate
dehydrogenase deficient red cells: resistance to infection by malarial
parasites. Science 164: 839-842, 1969.

200. MacDonald, D.; Town, M.; Mason, P.; Vulliamy, T.; Luzzatto, L.;
Goff, D. K.: Deficiency in red blood cells. (Letter) Nature 350:
115, 1991.

201. Maeda, M.; Constantoulakis, P.; Chen, C.-S.; Stamatoyannopoulos,
G.; Yoshida, A.: Molecular abnormalities of a human glucose-6-phosphate
dehydrogenase variant associated with undetectable enzyme activity
and immunologically cross-reacting material. Am. J. Hum. Genet. 51:
386-395, 1992.

202. Mamlok, R. J.; Mamlok, V.; Mills, G. C.; Daeschner, C. W., III;
Schmalstieg, F. C.; Anderson, D. C.: Glucose-6-phosphate dehydrogenase
deficiency, neutrophil dysfunction and Chromobacterium violaceum sepsis. J.
Pediat. 111: 852-854, 1987.

203. Mamlok, R. J.; Mills, G. C.; Goldblum, R. M.; Daeschner, C. W.
: Glucose-6-phosphate dehydrogenase Beaumont: a new variant with severe
enzyme deficiency and chronic nonspherocytic hemolytic anemia. Enzyme 34:
15-21, 1985.

204. Mandelli, F.; Amadori, S.; DeLaurenzi, A.; Kahn, A.; Isacchi,
G.; Papa, G.: Glucose-6-phosphate dehydrogenase Velletri: a new variant
with reduced activity in a patient with congenital non-spherocytic
haemolytic anemia. Acta Haemat. 57: 121-126, 1977.

205. Marks, P. A.; Banks, J.; Gross, R.: Genetic heterogeneity of
glucose-6-phosphate dehydrogenase deficiency. Nature 194: 454-456,
1962.

206. Martin, S. K.; Miller, L. H.; Alling, D.; Okoye, V. C.; Esan,
G. J. F.; Osunkoya, B. O.; Deane, M.: Severe malaria and glucose-6-phosphate-dehydrogenase
deficiency: a reappraisal of the malaria-G6PD hypothesis. Lancet 313:
524-526, 1979. Note: Originally Volume I.

207. Martini, G.; Toniolo, D.; Vulliamy, T.; Luzzatto, L.; Dono, R.;
Viglietto, G.; Paonessa, G.; D'Urso, M.; Persico, M. G.: Structural
analysis of the X-linked gene encoding human glucose 6-phosphate dehydrogenase. EMBO
J. 5: 1849-1855, 1986.

208. Mason, P. J.: New insights into G6PD deficiency. (Annotation) Brit.
J. Haemat. 94: 585-591, 1996.

209. Mason, P. J.; Stevens, D. J.; Luzzatto, L.; Brenner, S.; Aparicio,
S.: Genomic structure and sequence of the Fugu rubripes glucose-6-phosphate
dehydrogenase gene (G6PD). Genomics 26: 587-591, 1995.

210. Matsuoka, H.; Jichun, W.; Hirai, M.; Yoshida, S.; Arai, M.; Ishii,
A.; Baral, M. P.: Two cases of glucose-6-phophate (sic) dehydrogenase-deficient
Nepalese belonging to the G6PD Mediterranean-type, not India-Pakistan
sub-type but Mediterranean-Middle East sub-type. J. Hum. Genet. 48:
275-277, 2003.

211. Matsuoka, H.; Nguon, C.; Kanbe, T.; Jalloh, A.; Sato, H.; Yoshida,
S.; Hirai, M.; Arai, M.; Socheat, D.; Kawamoto, F.: Glucose-6-phosphate
dehydrogenase (G6PD) mutations in Cambodia: G6PD Viangchan (871G-A)
is the most common variant in the Cambodian population. J. Hum. Genet. 50:
468-472, 2005.

212. Matsuoka, H.; Wang, J.; Hirai, M.; Arai, M.; Yoshida, S.; Kobayashi,
T.; Jalloh, A.; Lin, K.; Kawamoto, F.: Glucose-6-phosphate dehydrogenase
(G6PD) mutations in Myanmar: G6PD Mahidol (487G-A) is the most common
variant in the Myanmar population. J. Hum. Genet. 49: 544-547, 2004.

213. McCann, S. R.; Smithwick, A. M.; Temperley, I. J.; Tipton, K.
: G6PD (Dublin): chronic non-spherocytic haemolytic anaemia resulting
from glucose-6-phosphate dehydrogenase deficiency in an Irish kindred. J.
Med. Genet. 17: 191-193, 1980.

214. McCurdy, P. R.: Use of genetic linkage for the detection of
female carriers of hemophilia. New Eng. J. Med. 285: 218-219, 1971.

215. McCurdy, P. R.; Blackwell, R. Q.; Todd, D.; Tso, S. C.; Tuchinda,
S.: Further studies on glucose-6-phosphate dehydrogenase deficiency
in Chinese subjects. J. Lab. Clin. Med. 75: 788-797, 1970.

216. McCurdy, P. R.; Kamel, K.; Selim, O.: Heterogeneity of red cell
glucose 6-phosphate dehydrogenase (G6PD) deficiency in Egypt. J.
Lab. Clin. Med. 84: 673-680, 1974.

217. McCurdy, P. R.; Kirkman, H. N.; Naiman, J. L.; Jim, R. T. S.;
Pickard, B. M.: A Chinese variant of glucose-6-phosphate dehydrogenase. J.
Lab. Clin. Med. 67: 374-385, 1966.

218. McCurdy, P. R.; Mahmood, L.: Red cell glucose-6-phosphate dehydrogenase
deficiency in Pakistan. J. Lab. Clin. Med. 76: 943-948, 1970.

219. McCurdy, P. R.; Maldonado, N. I.; Dillon, D. E.: Variants of
glucose-6-phosphate dehydrogenase (G-6-PD) associated with G-6-PD
deficiency in Puerto Ricans. J. Lab. Clin. Med. 82: 432-437, 1973.

220. McCurdy, P. R.; Maldonado, N. I.; Dillon, D. E.; Conrad, M. E.
: Variants of glucose-6-phosphate dehydrogenase (G-6-PD) associated
with G-6-PD deficiency in Puerto Ricans. J. Lab. Clin. Med. 82:
432-437, 1973.

221. Meloni, T.; Carta, F.; Forteleoni, G.; Carta, A.; Ena, F.; Meloni,
G. F.: Glucose 6-phosphate dehydrogenase deficiency and cataract
of patients in northern Sardinia. Am. J. Ophthal. 110: 661-664,
1990.

222. Mentzer, W. C., Jr.; Warner, R.; Addiego, J.; Smith, B.; Walter,
T.: G6PD San Francisco: a new variant of glucose-6-phosphate dehydrogenase
associated with congenital nonspherocytic hemolytic anemia. Blood 55:
195-198, 1980.

223. Mesbah-Namin, S. A.; Sanati, M. H.; Mowjoodi, A.; Mason, P. J.;
Vulliamy, T. J.; Noori-Daloii, M. R.: Three major glucose-6-phosphate
dehydrogenase-deficient polymorphic variants identified in Mazandaran
state of Iran. Brit. J. Haemat. 117: 763-764, 2002.

224. Miller, D. R.; Wollman, M. R.: A new variant of glucose 6-phosphate
dehydrogenase deficiency hereditary hemolytic anemia, G6PD Cornell:
erythrocyte, leukocyte and platelet studies. Blood 44: 277-284,
1974.

225. Mills, G. C.; Alperin, J. B.; Trimmer, K. B.: Studies on variant
glucose-6-phosphate dehydrogenase: G6PD Fort Worth. Biochem. Med. 13:
264-275, 1975.

226. Milner, G.; Delamore, I. W.; Yoshida, A.: G-6-PD Manchester:
a new variant associated with chronic nonspherocytic hemolytic anemia. Blood 43:
271-276, 1974.

227. Miwa, S.; Fujii, H.: Molecular basis of erythroenzymopathies
associated with hereditary hemolytic anemia: tabulation of mutant
enzymes. Am. J. Hemat. 51: 122-132, 1996.

228. Miwa, S.; Fujii, H.; Nakashima, K.; Miura, Y.; Yamada, K.; Hagiwara,
T.; Fukuda, M.: Three new electrophoretically normal glucose-6-phosphate
dehydrogenase variants associated with congenital nonspherocytic hemolytic
anemia found in Japan: G6PD Ogikubo, Yokohama, and Akita. Hum. Genet. 45:
11-17, 1978.

229. Miwa, S.; Fujii, H.; Nakatsuji, T.; Ishida, Y.; Oda, E.; Kaneto,
A.; Motokawa, M.; Ariga, Y.; Fukuchi, S.; Sasai, S.; Hiraoka, K.;
Kashii, H.; Kodama, T.: Four new electrophoretically slow-moving
glucose-6-phosphate dehydrogenase variants associated with congenital
nonspherocytic hemolytic anemia found in Japan: Gd(-) Kurume, Gd(-)
Fukushima, Gd(-) Yamaguchi, and Gd(-) Wakayama. Am. J. Hemat. 5:
131-138, 1978.

230. Miwa, S.; Nakashima, K.; Ono, J.; Fujii, H.; Suzuki, E.: Three
glucose 6-phosphate dehydrogenase variants found in Japan. Hum. Genet. 36:
327-334, 1977.

231. Miwa, S.; Ono, J.; Nakashima, K.; Abe, S.; Kageoka, T.; Shinohara,
K.; Isobe, J.; Yamaguchi, H.: Two new glucose 6-phosphate dehydrogenase
variants associated with congenital nonspherocytic hemolytic anemia
found in Japan: Gd(-) Tokushima and Gd(-) Tokyo. Am. J. Hemat. 1:
433-442, 1976.

232. Modiano, G.; Battistuzzi, G.; Esan, G. J. F.; Testa, U.; Luzzatto,
L.: Genetic heterogeneity of 'normal' human erythrocyte glucose-6-phosphate
dehydrogenase: an isoelectrophoretic polymorphism. Proc. Nat. Acad.
Sci. 76: 852-856, 1979.

233. Mohrenweiser, H. W.; Neel, J. V.: Frequency of thermostability
variants: estimation of total 'rare' variant frequency in human populations. Proc.
Nat. Acad. Sci. 78: 5729-5733, 1981.

234. Morelli, A.; Benatti, U.; Guida, L.; De Flora, A.: G6PD Cagliari:
a new low activity glucose 6-phosphate dehydrogenase variant characterized
by enhanced intracellular lability. Hum. Genet. 66: 62-65, 1984.

235. Morisaki, T.; Fujii, H.; Takegawa, S.; Tani, K.; Hirono, A.;
Takizawa, T.; Takahashi, K.; Shinogi, M.; Teshirogi, T.; Miwa, S.
: G6PD Sendagi: a new glucose-6-phosphate dehydrogenase variant associated
with congenital hemolytic anemia. Hum. Genet. 65: 214-215, 1983.

236. Nafa, K.; Reghis, A.; Osmani, N.; Baghli, L.; Benabadji, M.;
Kaplan, J.-C.; Vulliamy, T. J.; Luzzatto, L.: G6PD Aures: a new mutation
(48 ile-to-thr) causing mild G6PD deficiency is associated with favism. Hum.
Molec. Genet. 2: 81-82, 1993.

237. Nagel, R. L.; Ranney, H. M.: Genetic epidemiology of structural
mutations of the beta-globin gene. Semin. Hemat. 27: 342-359, 1990.

238. Nakai, T.; Yoshida, A.: G6PD Heian. A glucose-6-phosphate dehydrogenase
variant associated with hemolytic anemia found in Japan. Clin. Chim.
Acta 51: 199-203, 1974.

239. Nakashima, K.; Ono, J.; Abe, S.; Miwa, S.; Yoshida, A.: G6PD
Ube: a glucose 6-phosphate dehydrogenase variant found in four unrelated
Japanese families. Am. J. Hum. Genet. 29: 24-30, 1977.

240. Nakatsuji, T.; Miwa, S.: Incidence and characteristics of glucose-6-phosphate
dehydrogenase variants in Japan. Hum. Genet. 51: 297-305, 1979.

241. Nance, W. E.: Turner's syndrome, twinning, and an unusual variant
of glucose-6-phosphate dehydrogenase. Am. J. Hum. Genet. 16: 380-392,
1964.

242. Necheles, T. F.; Snyder, L. M.; Strauss, W.: Glucose-6-phosphate
dehydrogenase Boston. A new variant associated with congenital nonspherocytic
hemolytic disease. Humangenetik 13: 218-221, 1971.

243. Niazi, G.; Adeyokunu, A.; Westwood, B.; Beutler, E.: G6PD Aures:
a rare mutant of G6PD in Saudi Arabia: molecular and clinical presentations. Saudi
Med. J. 17: 311-314, 1996.

244. Ninfali, P.; Baronciani, L.; Bardoni, A.; Bresolin, N.: Muscle
expression of glucose-6-phosphate dehydrogenase deficiency in different
variants. Clin. Genet. 48: 232-237, 1995.

245. Ninokata, A.; Kimura, R.; Samakkarn, U.; Settheetham-Ishida,
W.; Ishida, T.: Coexistence of five G6PD variants indicates ethnic
complexity of Phuket islanders, Southern Thailand. J. Hum. Genet. 51:
424-428, 2006.

246. Notaro, R.; Afolayan, A.; Luzzatto, L.: Human mutations in glucose
6-phosphate dehydrogenase reflect evolutionary history. FASEB J. 14:
485-494, 2000.

247. Nowicki, L.; Strobel, S.; Martin, H.; Koschwitz, U.: Ueber eine
neue erythrocytaere glucose 6-phosphatdehydrogenase Variante, Typ
Frankfurt. Klin. Wschr. 52: 478-484, 1974.

248. Nsouly, G. M.; Prchal, J. T.: Characterization of a new G6PD
variant and its associated oxidative damage. Clin. Res. 29: 829,
1981.

249. O'Brien, S. J.: The extent and character of biochemical genetic
variation in the domestic cat. J. Hered. 71: 2-8, 1980.

250. Ogura, H.; Morisaki, T.; Tani, K.; Kanno, H.; Tsutsumi, H.; Takahashi,
K.; Miyamori, T.; Fujii, H.; Miwa, S.: A new glucose-6-phosphate
dehydrogenase variant (G6PD Tsukui) associated with congenital hemolytic
anemia. Hum. Genet. 78: 369-371, 1988.

251. Ohno, S.: Sex Chromosomes and Sex-linked Genes. Berlin and
New York: Springer (pub.) 1967.

252. Othieno-Obel, A.: East African variant of glucose-6-phosphate
dehydrogenase. East Afr. Med. J. 49: 230-234, 1972.

253. Pai, G. S.; Sprenkle, J. A.; Do, T. T.; Mareni, C. E.; Migeon,
B. R.: Localization of loci for hypoxanthine phosphoribosyltransferase
and glucose-6-phosphate dehydrogenase and biochemical evidence of
nonrandom X chromosome expression from studies of a human X-autosome
translocation. Proc. Nat. Acad. Sci. 77: 2810-2813, 1980.

254. Panich, V.: G6PD Intanon, a new glucose 6-phosphate dehydrogenase
variant. Humangenetik 21: 203-205, 1974.

255. Panich, V.: G6PD characterization in Thailand. Genetics 74
(suppl.): s208 only, 1973.

256. Panich, V.: G6PD variants in Laotians. Hum. Hered. 24: 285-290,
1974.

257. Panich, V.: Glucose-6-phosphate dehydrogenase in Thailand. Hum.
Genet. 53: 227-228, 1980.

258. Panich, V.; Bumrungtrakul, P.; Jitjai, C.; Kamolmatayakul, S.;
Khoprasert, B.; Klaisuvan, C.; Kongmuang, U.; Maneechai, P.; Pornpatkul,
M.; Ruengrairatanaroje, P.; Surapruk, P.; Viriyayudhakorn, S.: Glucose-6-phosphate
dehydrogenase deficiency in South Vietnamese. Hum. Hered. 30: 361-364,
1980.

259. Panich, V.; Na-Nakorn, S.: G6PD variants in Thailand. J. Med.
Assoc. Thai. 63: 537-543, 1980.

260. Panich, V.; Sungnate, T.: Characterization of glucose 6-phosphate
dehydrogenase in Thailand: the occurrence of 6 variants among 50 G6PD
deficient Thai. Humangenetik 18: 39-46, 1973.

261. Panich, V.; Sungnate, T.; Na-Nakorn, S.: Acute intravascular
hemolysis and renal failure in a new glucose 6-phosphate dehydrogenase
variant: G6PD Siriraj. J. Med. Assoc. Thai. 55: 726-731, 1972.

262. Panich, V.; Sungnate, T.; Wasi, P.; Na-Nakorn, S.: G-6-PD Mahidol:
the most common glucose-6-phosphate dehydrogenase variant in Thailand. J.
Med. Assoc. Thai. 55: 576-585, 1972.

263. Pawlak, A. L.; Mazurkiewicz, C. A.; Ordynski, J.; Ruzynkowa,
D.; Horst, A.: G6PD Poznan, variant with severe enzyme deficiency. Humangenetik 28:
163-165, 1975.

264. Pawlak, A. L.; Zagorski, Z.; Rozynkowa, D.; Horst, A.: Polish
variant of glucose-6-phosphate dehydrogenase (G-6-PD Lublin). Humangenetik 10:
340-343, 1970.

265. Pekrun, A.; Eber, S. W.; Schroter, W.: G6PD Avenches and G6PD
Moosburg: biochemical and erythrocyte membrane characterization. Blut 58:
11-14, 1989.

266. Perroni, L.; Tassara, P.; Baldi, M.; Reali, R.; Scartezzini,
P.: G6PD variants detected in Genoa area.In: Weatherall, D. J.; Fiorelli,
G.; Gorini, S.: Advances in Red Blood Cell Biology. New York: Raven
Press (pub.) 1982. Pp. 409-416.

267. Persico, M. G.; Toniolo, D.; Nobile, C.; D'Urso, M.; Luzzatto,
L.: cDNA sequences of human glucose 6-phosphate dehydrogenase cloned
in pBR322. Nature 294: 778-780, 1981.

268. Persico, M. G.; Viglietto, G.; Martini, G.; Toniolo, D.; Paonessa,
G.; Moscatelli, C.; Dono, R.; Vulliamy, T.; Luzzatto, L.; D'Urso,
M.: Isolation of human glucose-6-phosphate dehydrogenase (G6PD) cDNA
clones: primary structure of the protein and unusual 5-prime non-coding
region. Nucleic Acids Res. 14: 2511-2522, 1986. Note: Erratum: Nucleic
Acids Res. 14: 7822 only, 1986.

269. Picat, C.; Etiemble, J.; Boivin, P.; Le Prise, P.-Y.: Gd(-)
Rennes, a new deficient variant of glucose-6-phosphate dehydrogenase
associated with congenital nonspherocytic hemolytic anemia found in
France. Hum. Genet. 55: 125-127, 1980.

270. Pinto, P. V. C.; Newton, W. A., Jr.; Richardson, K. E.: Evidence
for four types of erythrocyte glucose-6-phosphate dehydrogenase from
G-6-PD deficient human subjects. J. Clin. Invest. 45: 823-831, 1966.

271. Poggi, V.: Personal Communication. London, England 1989.

272. Poon, M.-C.; Hall, K.; Scott, C. W.; Prchal, J. T.: G6PD Viangchan:
a new glucose 6-phosphate dehydrogenase variant from Laos. Hum. Genet. 78:
98-99, 1988.

273. Porter, I. H.; Boyer, S. H.; Watson-Williams, E. J.; Adam, A.;
Szeinberg, A.; Siniscalco, M.: Variation of glucose-6-phosphate dehydrogenase
in different populations. Lancet 283: 895-899, 1964. Note: Originally
Volume I.

274. Porter, I. H.; Schulze, J.; McKusick, V. A.: Genetical linkage
between the loci for glucose-6-phosphate dehydrogenase deficiency
and colour-blindness in American Negroes. Ann. Hum. Genet. 26: 107-122,
1962.

275. Prchal, J.; Moreno, H.; Conrad, M.; Vitek, A.: G-6-PD Dothan:
a new variant associated with chronic hemolytic anemia. I.R.C.S. 7:
348, 1979.

276. Prchal, J. T.: Personal Communication. Birmingham, Ala. 1985.

277. Prchal, J. T.; Crist, W. M.; Malluh, A.; Vitek, A.; Tauxe, W.
N.; Carroll, A. J.: A new glucose-6-phosphate dehydrogenase deficient
variant in a patient with Chediak-Higashi syndrome. Blood 56: 476-480,
1980.

278. Prchal, J. T.; Hall, K.; Csepreghy, M.; Lilly, M.; Berkow, R.;
Scott, C. W.: Two apparent glucose-6-phosphate dehydrogenase variants
in normal XY males: G6PD Alabama. Am. J. Med. 84: 517-523, 1988.

279. Ramot, B.; Ben-Bassat, I.; Shchory, M.: New glucose-6-phosphate
dehydrogenase variants observed in Israel and their association with
congenital nonspherocytic hemolytic disease. J. Lab. Clin. Med. 74:
895-901, 1969.

280. Ramot, B.; Brok, F.: A new glucose-6-phosphate dehydrogenase
mutant (Tel-Hashomer mutant). Ann. Hum. Genet. 28: 167-172, 1964.

281. Rattazzi, M. C.; Corash, L. M.; Van Zzanen, G. E.; Jaffe, E.
R.; Piomelli, S.: G6PD deficiency and chronic hemolysis: four new
mutants--relationships between clinical syndrome and enzyme kinetics. Blood 38:
205-218, 1971.

282. Rattazzi, M. C.; Lenzerini, L.; Meera Khan, P.; Luzzatto, L.
: Characterization of glucose-6-phosphate dehydrogenase variants.
II. G6PD Kephalonia, G6PD Attica, and G6PD 'Seattle-like' found in
Greece. Am. J. Hum. Genet. 21: 154-167, 1969.

283. Ravindranath, Y.; Beutler, E.: Two new variants of glucose-6-phosphate
dehydrogenase associated with hereditary non-spherocytic hemolytic
anemia: G6PD Wayne and G6PD Huron. Am. J. Hemat. 24: 357-363, 1987.

284. Reys, L.; Manso, C.; Stamatoyannopoulos, G.: Genetic studies
on Southeastern Bantu of Mozambique. I. Variants of glucose-6-phosphate
dehydrogenase. Am. J. Hum. Genet. 22: 203-215, 1970.

285. Rosenstraus, M.; Chasin, L. A.: Isolation of mammalian cell
mutants deficient in glucose-6-phosphate dehydrogenase activity: linkage
to hypoxanthine phosphoribosyl transferase. Proc. Nat. Acad. Sci. 72:
493-497, 1975.

286. Roth, E. F., Jr.; Raventos-Suarez, C.; Rinaldi, A.; Nagel, R.
L.: Glucose-6-phosphate dehydrogenase deficiency inhibits in vitro
growth of Plasmodium falciparum. Proc. Nat. Acad. Sci. 80: 298-299,
1983.

287. Roychoudhury, A. K.; Nei, M.: Human Polymorphic Genes: World
Distribution. New York: Oxford Univ. Press (pub.) 1988.

288. Ruwando, C.; Khea, S. C.; Snow, R. W.; Yates, S. N. R.; Kwiatkoweld,
D.; Gupta, S.; Warn, P.; Alisopp, G. E. M.; Gilbert, S. C.; Peschu,
N.; Newbold, C. I.; Greenwood, S. M.; Marsh, K.; Hill, A. V. S.:
Natural selection of hemi- and heterozygotes for G6PD deficiency in
Africa by resistance to severe malaria. Nature 376: 246-249, 1995.

289. Saenz, G. F.; Chaves, M.; Berrantes, A.; Elizondo, J.; Montero,
A. G.; Yoshida, A.: A glucose-6-phosphate dehydrogenase variant,
Gd(-) Santamaria found in Costa Rica. Acta Haemat. 72: 37-40, 1984.

290. Saidi, N.; Hors-Cayla, M. C.; Van Cong, N.; Benne, F.: Sheep
gene mapping by somatic cell hybridization. (Abstract) Cytogenet.
Cell Genet. 25: 200, 1979.

291. Samuel, A. P. W.; Saha, N.; Omer, A.; Hoffbrand, A. V.: Quantitative
expression of G6PD activity of different phenotypes of G6PD and haemoglobin
in a Sudanese population. Hum. Hered. 31: 110-115, 1981.

292. Sansone, G.; Perroni, L.; Testa, U.; Mareni, C.; Luzzatto, L.
: New genetic variants of glucose 6-phosphate dehydrogenase (G6PD)
in Italy. Ann. Hum. Genet. 45: 97-104, 1981.

293. Sansone, G.; Perroni, L.; Yoshida, A.: Glucose-6-phosphate dehydrogenase
variants from Italian subjects associated with severe neonatal jaundice. Brit.
J. Haemat. 31: 159-165, 1975.

294. Sansone, G.; Perroni, L.; Yoshida, A.; Dave, V.: A new glucose
6-phosphate dehydrogenase variant (Gd Trinacria) in two unrelated
families of Sicilian ancestry. Ital. J. Biochem. 26: 44-50, 1977.

295. Shatskaya, T. L.; Krasnopolskaya, K. D.; Annenkov, G. A.: A
description of new mutant forms of erythrocyte glucose-6-phosphate
dehydrogenase isolated at the territory of the Soviet Union. Genetika 11:
116-122, 1975.

296. Shatskaya, T. L.; Krasnopolskaya, K. D.; Idelson, L. J.: The
new form of glucose 6-phosphate dehydrogenase (G6PD 'Kaluga') from
erythrocytes of a patient with chronic non-spherocytic hemolytic anemia. Vopr.
Med. Khim. 22: 764-768, 1976.

297. Shatskaya, T. L.; Krasnopolskaya, K. D.; Idelson, L. J.: Mutant
forms of erythrocyte glucose 6-phosphate dehydrogenase in Ashkenazi:
description of two new variants, G6PD Kirovograd and G6PD Zhitomir. Humangenetik 33:
175-178, 1976.

298. Shatskaya, T. L.; Krasnopolskaya, K. D.; Tzoneva, M.; Mavrudieva,
M.; Toncheva, D.: Variants of erythrocyte glucose-6-phosphate dehydrogenase
(G6PD) in Bulgarian populations. Hum. Genet. 54: 115-117, 1980.

299. Shatskaya, T. L.; Krasnopolskaya, K. D.; Zakharova, T. V.: Regularities
of distribution of Gd-alleles in Azerbaijan. II. Identification of
G6PD mutant forms. Genetika 16: 2217-2225, 1980.

300. Shows, T. B.; Brown, J. A.: Human X-linked genes regionally
mapped utilizing X-autosome translocations and somatic cell hybrids. Proc.
Nat. Acad. Sci. 72: 2125-2129, 1975.

301. Shows, T. B.; Brown, J. A.; Chapman, V. M.: Comparative gene
mapping of HPRT, G6PD and PGK in man, mouse, and Muntjac deer. Birth
Defects Orig. Art. Ser. XII(7): 436-439, 1976.

302. Shows, T. B.; Tashian, R. E.; Brewer, G. J.: Erythrocyte glucose-6-phosphate
dehydrogenase in Caucasians: new inherited variant. Science 145:
1056-1057, 1964.

303. Sidi, Y.; Aderka, D.; Brok-Simoni, F.; Benjamin, D.; Ramot, B.;
Pinkhas, J.: Viral hepatitis with extreme hyperbilirubinemia, massive
hemolysis and encephalopathy in a patient with a new G6PD variant. Isr.
J. Med. Sci. 16: 130-133, 1980.

304. Siegel, N. H.; Beutler, E.: Hemolytic anemia caused by G-6-PD
Carswell, a new variant. Ann. Intern. Med. 75: 437-439, 1971.

305. Smith, J. E.; Ryer, K.; Wallace, L.: Glucose-6-phosphate dehydrogenase
deficiency in a dog. Enzyme 21: 379-382, 1976.

306. Snyder, L. M.; Necheles, T. F.; Reddy, W. J.: G-6-PD Worcester:
a new variant, associated with X-linked optic atrophy. Am. J. Med. 49:
125-132, 1970.

307. Stamatoyannopoulos, G.; Kotsakis, P.; Voigtlander, V.; Akrivakis,
A.; Motulsky, A. G.: Electrophoretic diversity of glucose-6-phosphate
dehydrogenase among Greeks. Am. J. Hum. Genet. 22: 587-596, 1970.

308. Stamatoyannopoulos, G.; Voigtlander, V.; Akrivakis, A.: Thessaly
variant of glucose-6-phosphate dehydrogenase. Humangenetik 9: 23-25,
1970.

309. Stamatoyannopoulos, G.; Voigtlander, V.; Kotsakis, P.; Akrivakis,
A.: Genetic diversity of the 'Mediterranean' glucose-6-phosphate
dehydrogenase deficiency phenotype. J. Clin. Invest. 50: 1253-1261,
1971.

310. Stamatoyannopoulos, G.; Yoshida, A.; Bacopoulos, C.; Motulsky,
A. G.: Athens variant of glucose-6-phosphate dehydrogenase. Science 157:
831-833, 1967.

311. Stevens, D. J.; Wanachiwanawin, W.; Mason, P. J.; Vulliamy, T.
J.; Luzzatto, L.: G6PD Canton a common deficient variant in South
East Asia caused by a 459 arg-to-leu mutation. Nucleic Acids Res. 18:
7190, 1990.

312. Stocco dos Santos, R. C.; Barretto, O. C. O.; Nonoyama, K.; Castro,
N. H. C.; Ferraz, O. P.; Walter-Moura, J.; Vescio, C. C. S.; Becak,
W.: X-linked syndrome: mental retardation, hip luxation, and G6PD
variant (Gd(+) Butantan). Am. J. Med. Genet. 39: 133-136, 1991.

313. Stocco dos Santos, R. C.; Castro, N. H. C.; Holmes, A. L.; Becak,
W.; Tackels-Horne, D.; Lindsey, C. J.; Lubs, H. A.; Stevenson, R.
E.; Schwartz, C. E.: Stocco dos Santos X-linked mental retardation
syndrome: clinical elucidation and localization to Xp11.3-Xq21.3. Am.
J. Med. Genet. 118A: 255-259, 2003.

314. Streiff, F.; Vigneron, C.: Anemie hemolytique chronique par
deficit en glucose 6-phosphate deshydrogenase dans une famille d'origine
Lorraine. Nouv. Rev. Franc. Hemat. 11: 279-290, 1971.

315. Takahashi, K.; Fujii, H.; Takegawa, S.; Tani, K.; Hirono, A.;
Takizawa, T.; Kawakatsu, T.; Miwa, S.: A new glucose-6-phosphate
dehydrogenase variant (G6PD Nagano) associated with congenital hemolytic
anemia. Hum. Genet. 62: 368-370, 1982.

316. Takizawa, T.; Fujii, H.; Takegawa, S.; Takahashi, K.; Hirono,
A.; Morisaki, T.; Kanno, H.; Oka, R.; Yoshioka, H.; Miwa, S.: A unique
electrophoretic slow-moving glucose 6-phosphate dehydrogenase variant
(G6PD Asahikawa) with a markedly acidic pH optimum. Hum. Genet. 68:
70-72, 1984.

317. Takizawa, T.; Huang, I.-Y.; Ikuta, T.; Yoshida, A.: Human glucose-6-phosphate
dehydrogenase: primary structure and cDNA cloning. Proc. Nat. Acad.
Sci. 83: 4157-4161, 1986.

318. Takizawa, T.; Yoneyama, Y.; Miwa, S.; Yoshida, A.: A single
nucleotide base transition is the basis of the common human glucose-6-phosphate
dehydrogenase variant A(+). Genomics 1: 228-231, 1987.

319. Takizawa, T.; Yoshida, A.: Molecular abnormality of the common
glucose-6-phosphate dehydrogenase variant, G6PD A(+), and restriction-fragment-length
polymorphism. (Abstract) Am. J. Hum. Genet. 41: A241, 1987.

320. Talalak, P.; Beutler, E.: G-6-PD Bangkok: a new variant found
in congenital nonspherocytic hemolytic disease (CNHD). Blood 33:
772-776, 1969.

321. Tanaka, K. R.; Beutler, E.: Hereditary hemolytic anemia due
to glucose-6-phosphate dehydrogenase Torrance: a new variant. J.
Lab. Clin. Med. 73: 657-667, 1969.

322. Tang, T. K.; Huang, C.-S.; Huang, M. J.; Tam, K.-B.; Yeh, C.-H.;
Tang, C.-J. C.: Diverse point mutations result in glucose-6-phosphate
dehydrogenase (G6PD) polymorphism in Taiwan. Blood 79: 2135-2140,
1992.

323. Testa, U.; Meloni, T.; Lania, A.; Battistuzzi, G.; Cutillo, S.;
Luzzatto, L.: Genetic heterogeneity of glucose-6-phosphate dehydrogenase
deficiency in Sardinia. Hum. Genet. 56: 99-105, 1980.

324. Thigpen, J. T.; Steinberg, M. H.; Beutler, E.; Gillespie, G.
T., Jr.; Dreiling, B. J.; Morrison, F. S.: Glucose-6-phosphate dehydrogenase
Jackson, a new variant associated with hemolytic anemia. Acta Haemat. 51:
310-314, 1974.

325. Tishkoff, S. A.; Varkonyi, R.; Cahinhinan, N.; Abbes, S.; Argyropoulos,
G.; Destro-Bisol, G.; Drousiotou, A.; Dangerfield, B.; Lefranc, G.;
Loiselet, J.; Piro, A.; Stoneking, M.; Tagarelli, A.; Tagarelli, G.;
Touma, E. H.; Williams, S. M.; Clark, A. G.: Haplotype diversity
and linkage disequilibrium at human G6PD: recent origin of alleles
that confer malarial resistance. Science 293: 455-462, 2001.

326. Tokarev, Y. N.; Chernyak, N. B.; Batischev, A. I.; Lanzina, N.
V.; Alexeyev, G. A.: Etude des proprietes electrophoretiques et cinetiques
de la glucose-6-phosphate deshydrogenase (Gd) d'erythrocytes dans
les deficits hereditaires de l'enzyme: description d'une nouvelle
variante de glucose-6-phosphate deshydrogenase: la Gd Kremenchug. Nouv.
Rev. Franc. Hemat. 20: 557-564, 1978.

327. Toncheva, D.: Variants of glucose-6-phosphate dehydrogenase
in a Vietnamese population. Hum. Hered. 36: 348-351, 1986.

328. Toncheva, D.; Tzoneva, M.: Genetic polymorphism of G6PD in a
Bulgarian population. Hum. Genet. 67: 340-342, 1984.

329. Toniolo, D.; Martini, G.; Migeon, B. R.; Dono, R.: Expression
of the G6PD locus on the human X chromosome is associated with demethylation
of three CpG islands within 100 kb of DNA. EMBO J. 7: 401-406, 1988.

330. Town, M.; Athanasiou-Metaxa, M.; Luzzatto, L.: Intragenic interspecific
complementation of glucose 6-phosphate dehydrogenase in human-hamster
cell hybrids. Somat. Cell Molec. Genet. 16: 97-108, 1990.

331. Town, M.; Bautista, J. M.; Mason, P. J.; Luzzatto, L.: Both
mutations in G6PD A- are necessary to produce the G6PD deficient phenotype. Hum.
Molec. Genet. 1: 171-174, 1992.

332. Usanga, E. A.; Bienzle, U.; Cancedda, K.; Fasuan, F. A.; Ajayi,
O.; Luzzatto, L.: Genetic variants of human erythrocyte glucose 6-phosphate
dehydrogenase: new variants in West Africa characterized by column
chromatography. Ann. Hum. Genet. 40: 279-286, 1977.

333. Vaca, G.; Ibarra, B.; Garcia Cruz, D.; Medina, C.; Romero, F.;
Cantu, J. M.; Beutler, E.: G-6-PD Jalisco and G-6-PD Morelia: two
new Mexican variants. Hum. Genet. 71: 82-85, 1985.

334. Vaca, G.; Ibarra, B.; Romero, F.; Olivares, N.; Cantu, J. M.;
Beutler, E.: G-6-PD Guadalajara: a new mutant associated with chronic
nonspherocytic hemolytic anemia. Hum. Genet. 61: 175-176, 1982.

335. van Bruggen, R.; Bautista, J. M.; Petropoulou, T.; de Boer, M.;
van Zwieten, R.; Gomez-Gallego, F.; Belohradsky, B. H.; Hartwig, N.
G.; Stevens, D.; Mason, P. J.; Roos, D.: Deletion of leucine 61 in
glucose-6-phosphate dehydrogenase leads to chronic nonspherocytic
anemia, granulocyte dysfunction, and increased susceptibility to infections. Blood 100:
1026-1030, 2002.

336. Ventura, A.; Panizon, F.; Soranzo, M. R.; Veneziano, G.; Sansone,
G.; Testa, U.; Luzzatto, L.: Congenital dyserythropoietic anaemia
type II associated with a new type of G6PD deficiency (G6PD Gabrovizza). Acta
Haemat. 71: 227-234, 1984.

337. Vergnes, H.; Gherardi, M.; Bouloux, C.: Erythrocyte glucose-6-phosphate
dehydrogenase in the Niokolonko (Malinke of the Niokolo) of the Eastern
Senegal: identification of a slow variant with normal activity (Tacoma-like). Hum.
Hered. 25: 80-87, 1975.

338. Vergnes, H.; Gherardi, M.; Quilici, J. C.; Yoshida, A.; Giacardy,
R.: G6PD Luz-Saint-Sauveur: a new variant with abnormal electrophoretic
mobility, mild enzyme deficiency and absence of hemolytic disorders. I.R.C.S. 7:
14, 1973.

339. Vergnes, H.; Gherardi, M.; Yoshida, A.: G6PD Lozere and Trinacria-like:
segregation of two non-hemolytic variants in a French family. Hum.
Genet. 34: 293-298, 1976.

340. Vergnes, H.; Ribet, A.; Bommelaer, G.; Amadieu, J.; Brun, H.
: GD(-) Muret and GD(-) Colomiers, two new variants of glucose-6-phosphate
dehydrogenase associated with favism. Hum. Genet. 57: 332-334, 1981.

341. Vergnes, H.; Yoshida, A.; Gourdin, D.; Gherardi, M.; Bierme,
R.; Ruffie, J.: Glucose 6-phosphate dehydrogenase Toulouse: a new
variant with marked instability and severe deficiency discovered in
a family of Mediterranean ancestry. Acta Haemat. 51: 240-249, 1974.

342. Viglietto, G.; Montanaro, V.; Calabro, V.; Vallone, D.; D'Urso,
M.; Persico, M. G.; Battistuzzi, G.: Common glucose-6-phosphate dehydrogenase
(G6PD) variants from the Italian population: biochemical and molecular
characterization. Ann. Hum. Genet. 54: 1-15, 1990.

343. Vives-Corrons, J.-L.; Kuhl, W.; Pujades, M. A.; Beutler, E.:
Molecular genetics of the glucose-6-phosphate dehydrogenase (G6PD)
Mediterranean variant and description of a new G6PD mutant, G6PD Andalus(1361A). Am.
J. Hum. Genet. 47: 575-579, 1990.

344. Vives-Corrons, J. L.; Feliu, E.; Pujades, M. A.; Cardellach,
F.; Rozman, C.; Carreras, A.; Jou, J. M.; Vallespi, M. T.; Zuazu,
F. J.: Severe glucose-6-phosphate dehydrogenase (G6PD) deficiency
associated with chronic hemolytic anemia, granulocyte dysfunction,
and increased susceptibility to infections: description of a new molecular
variant (G6PD Barcelona). Blood 59: 428-434, 1982.

345. Vives-Corrons, J. L.; Pujades, A.: Heterogeneity of 'Mediterranean
type' glucose-6-phosphate dehydrogenase (G6PD) deficiency in Spain
and description of two new variants associated with favism. Hum.
Genet. 60: 216-221, 1982.

346. Vives-Corrons, J. L.; Pujades, A.; Curia, M. D.: Caracterizacion
molecular de la glucosa-6-fosfato deshidrogenasa (G6PD) en 24 casos
de deficit enzimatico y descripcion de una nueva variante (G6PD-Betica). Sangre 25:
1049-1064, 1980.

347. Vives-Corrons, J. L.; Pujades, M. A.; Petit, J.; Colomer, D.;
Corbella, M.; Aguilar i Bascompte, J. L.; Merino, A.: Chronic nonspherocytic
hemolytic anemia (CNSHA) and glucose 6 phosphate dehydrogenase (G6PD)
deficiency in a patient with familial amyloidotic polyneuropathy (FAP):
molecular study of a new variant (G6PD Clinic) with markedly acidic
pH optimum. Hum. Genet. 81: 161-164, 1989.

348. Vulliamy, T.; Beutler, E.; Luzzatto, L.: Variants of glucose-6-phosphate
dehydrogenase are due to missense mutations spread throughout the
coding region of the gene. Hum. Mutat. 2: 159-167, 1993.

349. Vulliamy, T.; Mason, P.; Luzzatto, L.: The molecular basis of
glucose-6-phosphate dehydrogenase deficiency. Trends Genet. 8: 138-143,
1992.

350. Vulliamy, T.; Rovira, A.; Yusoff, N.; Colomer, D.; Luzzatto,
L.; Vives-Corrons, J.-L.: Independent origin of single and double
mutations in the human glucose 6-phosphate dehydrogenase gene. Hum.
Mutat. 8: 311-318, 1996.

351. Vulliamy, T. J.: Personal Communication. London, England
1989.

352. Vulliamy, T. J.; D'Urso, M.; Battistuzzi, G.; Estrada, M.; Foulkes,
N. S.; Martini, G.; Calabro, V.; Poggi, V.; Giordano, R.; Town, M.;
Luzzatto, L.; Persico, M. G.: Diverse point mutations in the human
glucose-6-phosphate dehydrogenase gene cause enzyme deficiency and
mild or severe hemolytic anemia. Proc. Nat. Acad. Sci. 85: 5171-5175,
1988.

353. Vulliamy, T. J.; Kaeda, J. S.; Ait-Chafa, D.; Mangerini, R.;
Roper, D.; Barbot, J.; Mehta, A. B.; Athanassiou-Metaxa, M.; Luzzatto,
L.; Mason, P. J.: Clinical and haematological consequences of recurrent
G6PD mutations and a single new mutation causing chronic nonspherocytic
haemolytic anaemia. Brit. J. Haemat. 101: 670-675, 1998.

354. Vulliamy, T. J.; Othman, A.; Town, M.; Nathwani, A.; Falusi,
A. G.; Mason, P. J.; Luzzatto, L.: Polymorphic sites in the African
population detected by sequence analysis of the glucose-6-phosphate
dehydrogenase gene outline the evolution of the variants A and A-. Proc.
Nat. Acad. Sci. 88: 8568-8571, 1991.

355. Vulliamy, T. J.; Wanachiwanawin, W.; Mason, P. J.; Luzzatto,
L.: G6PD Mahidol, a common deficient variant in South East Asia is
caused by a (163)glycine-to-serine mutation. Nucleic Acids Res. 17:
5868, 1989.

356. Vuopio, P.; Harkonen, M.; Helske, T.; Naeveri, H.: Red cell
glucose-6-phosphate dehydrogenase deficiency in Finland: characterization
of a new variant with severe enzyme deficiency. Scand. J. Haemat. 15:
145-152, 1975.

357. Vuopio, P.; Harkonen, M.; Johnsson, P.; Nuutinen, M.: Red cell
glucose-phosphate dehydrogenase deficiency in Finland. Ann. Clin.
Res. 5: 168-178, 1973.

358. Waitz, R.; Boivin, P.; Oberling, F.; Casenave, J. P.; North,
M. L.; Mayer, S.: Variante Gd(-) Strasbourg de la glucose-6-phosphate
dehydrogenase. Nouv. Rev. Franc. Hemat. 10: 312-314, 1970.

359. Weimer, T. A.; Salzano, F. M.; Hutz, M. H.: Erythrocyte isozymes
and hemoglobin types in a southern Brazilian population. J. Hum.
Evol. 10: 319-328, 1981.

360. Weimer, T. A.; Schuler, L.; Beutler, E.; Salzano, F. M.: Gd(+)
Laguna, a new rare glucose-6-phosphate dehydrogenase variant from
Brazil. Hum. Genet. 65: 402-404, 1984.

361. Weinreich, J.; Busch, D.; Gottstein, U.; Schaefer, J.; Rohr,
J.: Ueber zwei neue Faelle von hereditaerer nichtsphaerocytaerer
haemolytischer Anaemie bei glucose-6-phosphat-dehydrogenase-Defekt
in einer Nord Deutschen Familie. Klin. Wschr. 46: 146-149, 1968.

362. Welch, S. G.; McGregor, I. A.; Williams, K.: A new variant of
human erythrocyte G6PD occurring at a high frequency amongst the population
of two villages in The Gambia, West Africa. Hum. Genet. 40: 305-309,
1978.

363. Westring, D. W.; Pisciotta, A. V.: Anemia, cataracts, and seizures
in patients with glucose-6-phosphate dehydrogenase deficiency. Arch.
Intern. Med. 118: 385-390, 1966.

364. WHO: Scientific group on the standardization of procedures
for the study of glucose-6-phosphate dehydrogenase. WHO Techn. Rep.
(pub.) Ser. No. 366: 1967.

365. WHO: Nomenclature of glucose-6-phosphate dehydrogenase in
man. Bull. WHO 36: 319-322, 1967. Note: See Also: Canad. Med. Assoc.
J. 97: 422-424, 1967.

366. Wilson, W. W.: Congenital hemolytic anemia due to a deficiency
of glucose 6-phosphate dehydrogenase. Rocky Mt. Med. J. 73: 160-162,
1976.

367. Witt, I.; Yoshioka, S.: Biochemical characterization of a glucose-6-phosphate
dehydrogenase variant with favism: G-6-PD Zaehringen. Klin. Wschr. 50:
205-209, 1972.

368. Wong, P. W. K.; Shih, L.-Y.; Hsia, D. Y. Y.: Characterization
of glucose-6-phosphate dehydrogenase among Chinese. Nature 208:
1323-1324, 1965.

369. Yermakov, N.; Tokarev, J.; Chernjak, N.; Schoenian, G.; Grieger,
M.; Guckler, G.; Jacobasch, G.; Mahmudova, M.; Bahramov, S.: New
stable mutant Gd(-) variants: G6PD Tashkent and G6PD Nucus: molecular
basis of hereditary enzyme deficiency. Acta Biol. Med. Ger. 40:
559-562, 1981.

370. Yoshida, A.: A single amino acid substitution (asparagine to
aspartic acid) between normal (B plus) and the common Negro variant
(A plus) of human glucose-6-phosphate dehydrogenase. Proc. Nat. Acad.
Sci. 57: 835-840, 1967.

371. Yoshida, A.: Human glucose-6-phosphate dehydrogenase: purification
and characterization of Negro type variant (A+) and comparison with
normal enzyme (B+). Biochem. Genet. 1: 81-99, 1967.

372. Yoshida, A.: Amino acid substitution (histidine to tyrosine)
in a glucose-6-phosphate dehydrogenase variant (G6PD Hektoen) associated
with over-production. J. Mol. Biol. 52: 483-490, 1970.

373. Yoshida, A.: Personal Communication. Duarte, Calif. 2/26/1996.

374. Yoshida, A.; Baur, E. W.; Motulsky, A. G.: A Philippino glucose-6-phosphate
dehydrogenase variant (G6PD Union) with enzyme deficiency and altered
substrate specificity. Blood 35: 506-513, 1970.

375. Yoshida, A.; Beutler, E.: Human glucose-6-phosphate dehydrogenase
variants: a supplementary tabulation. Ann. Hum. Genet. 41: 347-355,
1978.

376. Yoshida, A.; Beutler, E.; Motulsky, A. G.: Table of human glucose-6-phosphate
dehydrogenase variants. Bull. WHO 45: 243-253, 1971.

377. Yoshida, A.; Stamatoyannopoulos, G.; Motulsky, A. G.: Negro
variant of glucose-6-phosphate dehydrogenase deficiency (A-) in man. Science 155:
97-99, 1967.

378. Yoshida, A.; Takizawa, T.: The same extra FokI cleavage site
exists in glucose-6-phosphate dehydrogenase variants A(+) and A(-). Am.
J. Hum. Genet. 43: 131-133, 1988.

379. Yoshida, A.; Takizawa, T.; Prchal, J. T.: RFLP of the X chromosome-linked
glucose-6-phosphate dehydrogenase locus in blacks. Am. J. Hum. Genet. 42:
872-876, 1988.

380. Zuo, L.; Chen, E.; Du, C. S.; Chang, C. N.; Chiu, D. T. Y.:
Genetic study of Chinese G6PD variants by direct PCR sequencing. (Abstract) Blood 76
(suppl. 1): 51A, 1990.

*FIELD* CN
Carol A. Bocchini - updated: 10/24/2013
Patricia A. Hartz - updated: 7/11/2013
Ada Hamosh - updated: 1/6/2010
Cassandra L. Kniffin - updated: 2/12/2009
Marla J. F. O'Neill - updated: 11/17/2008
Cassandra L. Kniffin - updated: 1/14/2008
Marla J. F. O'Neill - updated: 4/12/2007
Cassandra L. Kniffin - updated: 7/14/2006
Cassandra L. Kniffin - updated: 6/26/2006
Cassandra L. Kniffin - updated: 3/9/2006
Marla J. F. O'Neill - updated: 1/18/2006
Victor A. McKusick - updated: 12/16/2005
Victor A. McKusick - updated: 1/11/2005
Victor A. McKusick - updated: 1/3/2005
Victor A. McKusick - updated: 8/19/2003
Victor A. McKusick - updated: 4/24/2003
Victor A. McKusick - updated: 3/4/2003
Victor A. McKusick - updated: 1/14/2003
Victor A. McKusick - updated: 10/22/2002
Victor A. McKusick - updated: 9/12/2002
Victor A. McKusick - updated: 4/23/2002
Victor A. McKusick - updated: 4/4/2002
Deborah L. Stone - updated: 10/8/2001
Ada Hamosh - updated: 9/24/2001
Ada Hamosh - updated: 8/27/2001
Victor A. McKusick - updated: 7/13/2000
Victor A. McKusick - updated: 4/26/2000
Victor A. McKusick - updated: 3/15/1999
Victor A. McKusick - updated: 11/12/1998
Victor A. McKusick - updated: 10/13/1998
Victor A. McKusick - updated: 6/25/1998
Victor A. McKusick - updated: 3/24/1998
Michael J. Wright - updated: 9/25/1997
Victor A. McKusick - updated: 9/19/1997
Victor A. McKusick - updated: 3/18/1997
Moyra Smith - updated: 11/12/1996
Alan F. Scott - updated: 12/14/1995

*FIELD* CD
Victor A. McKusick: 7/6/1987

*FIELD* ED
joanna: 12/09/2013
mgross: 10/25/2013
carol: 10/25/2013
carol: 10/24/2013
mgross: 7/11/2013
carol: 4/18/2013
terry: 3/14/2013
terry: 12/20/2012
alopez: 3/5/2012
mgross: 7/7/2011
carol: 4/7/2011
terry: 11/8/2010
terry: 10/12/2010
alopez: 1/19/2010
terry: 1/6/2010
terry: 6/12/2009
terry: 3/27/2009
wwang: 2/19/2009
ckniffin: 2/12/2009
wwang: 11/24/2008
terry: 11/21/2008
terry: 11/17/2008
wwang: 1/31/2008
ckniffin: 1/14/2008
wwang: 4/18/2007
terry: 4/12/2007
alopez: 2/1/2007
carol: 7/21/2006
ckniffin: 7/14/2006
wwang: 7/13/2006
ckniffin: 6/26/2006
wwang: 5/25/2006
ckniffin: 3/9/2006
wwang: 1/18/2006
wwang: 12/28/2005
terry: 12/16/2005
terry: 2/7/2005
tkritzer: 1/21/2005
terry: 1/11/2005
wwang: 1/6/2005
terry: 1/3/2005
terry: 5/21/2004
joanna: 3/17/2004
carol: 2/23/2004
cwells: 11/7/2003
mgross: 8/21/2003
terry: 8/19/2003
carol: 4/24/2003
terry: 4/24/2003
cwells: 3/11/2003
terry: 3/4/2003
carol: 1/22/2003
tkritzer: 1/17/2003
terry: 1/14/2003
tkritzer: 10/29/2002
tkritzer: 10/24/2002
terry: 10/22/2002
carol: 9/18/2002
tkritzer: 9/13/2002
tkritzer: 9/12/2002
carol: 7/2/2002
alopez: 5/3/2002
terry: 4/23/2002
cwells: 4/15/2002
cwells: 4/9/2002
terry: 4/4/2002
carol: 10/8/2001
alopez: 9/25/2001
terry: 9/24/2001
alopez: 8/30/2001
terry: 8/27/2001
alopez: 7/21/2000
terry: 7/13/2000
mcapotos: 5/24/2000
mcapotos: 5/19/2000
terry: 4/26/2000
carol: 9/10/1999
joanna: 6/18/1999
carol: 5/27/1999
carol: 3/18/1999
terry: 3/15/1999
carol: 11/19/1998
terry: 11/12/1998
carol: 10/20/1998
carol: 10/18/1998
terry: 10/13/1998
dkim: 7/21/1998
alopez: 6/26/1998
terry: 6/25/1998
alopez: 3/31/1998
terry: 3/24/1998
dholmes: 2/10/1998
alopez: 1/14/1998
terry: 1/12/1998
dholmes: 1/9/1998
alopez: 11/10/1997
terry: 9/19/1997
alopez: 7/28/1997
terry: 7/9/1997
mark: 7/7/1997
alopez: 6/27/1997
joanna: 6/23/1997
carol: 6/23/1997
mark: 6/16/1997
mark: 3/18/1997
terry: 3/11/1997
terry: 1/27/1997
jamie: 1/21/1997
terry: 1/14/1997
joanna: 1/1/1997
terry: 11/19/1996
mark: 11/12/1996
mark: 9/18/1996
mark: 7/9/1996
mark: 3/31/1996
terry: 3/21/1996
joanna: 3/15/1996
mark: 3/1/1996
terry: 3/1/1996
mark: 2/19/1996
terry: 2/15/1996
terry: 2/6/1996
mark: 1/17/1996
joanna: 12/18/1995
mark: 12/15/1995
terry: 12/14/1995
mark: 7/19/1995
carol: 2/27/1995
davew: 8/5/1994
jason: 7/1/1994
pfoster: 4/22/1994
terry: 4/20/1994

RBCC Red Blood Cell Collection

Full text data of G6PD