RBCC Red Blood Cell Collection

HBD [Confidence: high (present in two of the MS resources)]
Hemoglobin subunit delta (Delta-globin; Hemoglobin delta chain)
Note: presumably soluble (membrane word is not in UniProt keywords or features)

UniProt P02042
ID HBD_HUMAN Reviewed; 147 AA.
AC P02042; Q3Y5H3; Q8WXT7;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 2.
DT 22-JAN-2014, entry version 143.
DE RecName: Full=Hemoglobin subunit delta;
DE AltName: Full=Delta-globin;
DE AltName: Full=Hemoglobin delta chain;
GN Name=HBD;
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 [GENOMIC DNA].
RX PubMed=7438204; DOI=10.1016/0092-8674(80)90427-4;
RA Spritz R.A., Deriel J.K., Forget B.G., Weissman S.M.;
RT "Complete nucleotide sequence of the human delta-globin gene.";
RL Cell 21:639-646(1980).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT SER-5.
RA Webster M.T., Harding R.M., Wells R.S., Clegg J.B.;
RT "Heterogeneous patterns of sequence variation in the human beta-globin
RT gene cluster.";
RL Submitted (JAN-2001) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Lee T., Gubin A., Miller J.L.;
RT "Alternate delta globin transcript.";
RL Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT TROODOS CYS-117.
RC TISSUE=Blood;
RX PubMed=16370491; DOI=10.1080/03630260500310828;
RA Eram S.M., Azimifar S.B., Abolghassemi H., Foulady P., Lotfi V.,
RA Masroury M., Hosseini M., Abdolhosseini A.;
RT "The IVS-II-1(G>A) betao-thalassemia mutation in cis with HbA2-Troodos
RT [Delta 116 (G18) Arg>Cys (CGC>TGC)] causes a complex prenatal
RT diagnosis in an Iranian family.";
RL Hemoglobin 29:289-292(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Blood;
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 [6]
RP PROTEIN SEQUENCE OF 2-147.
RX PubMed=680638;
RA Braunitzer G., Schrank B., Stangl A., Grillemeier M.;
RT "Hemoglobins, XXIII. Note on the sequence of the delta-chains of human
RT hemoglobin.";
RL Hoppe-Seyler's Z. Physiol. Chem. 359:777-783(1978).
RN [7]
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 [8]
RP VARIANT DELTA' ARG-17.
RX PubMed=5956309; DOI=10.1038/2091217a0;
RA Ball E.W., Meynell M.J., Beale D., Kynoch P., Lehmann H.,
RA Strelton A.O.W.;
RT "Haemoglobin A2: alpha-2-delta-2-16 glycine-->arginine.";
RL Nature 209:1217-1218(1966).
RN [9]
RP VARIANT BABINGA ASP-137.
RX PubMed=5678016; DOI=10.1038/2191360a0;
RA de Jong W.W.W., Bernini L.F.;
RT "Haemoglobin Babinga (delta 136 glycine-aspartic acid): a new delta
RT chain variant.";
RL Nature 219:1360-1362(1968).
RN [10]
RP VARIANT NYU LYS-13.
RX PubMed=5824070; DOI=10.1172/JCI106171;
RA Ranney H.M., Jacobs A.S., Ramot B., Bradley T.B. Jr.;
RT "Hemoglobin NYU, a delta chain variant, alpha 2 delta 2 Lys.";
RL J. Clin. Invest. 48:2057-2062(1969).
RN [11]
RP VARIANT INDONESIA ARG-70.
RX PubMed=4995018;
RA Lie-Injo L.E., Pribadi W., Westendorp-Boerma F., Efremov G.D.,
RA Wilson J.B., Reynolds C.A., Huisman T.H.J.;
RT "Hemoglobin A2-Indonesia or alpha 2 delta 2 69(E13) Gly-->Arg.";
RL Biochim. Biophys. Acta 229:335-342(1971).
RN [12]
RP VARIANT MELBOURNE LYS-44.
RX PubMed=4850239;
RA Sharma R.S., Harding D.L., Wong S.D., Wilson J.B., Gravely M.E.,
RA Huisman T.H.J.;
RT "A new delta chain variant, haemoglobin-A2-Melbourne or alpha2 delta2
RT 43Glu-Lys(CD2).";
RL Biochim. Biophys. Acta 359:233-235(1974).
RN [13]
RP VARIANT COBURG HIS-117.
RX PubMed=1148221;
RA Sharma R.S., Williams L., Wilson J.B., Huisman T.H.J.;
RT "Hemoglobin-A2-Coburg or alpha2delta2116Arg leads to His (G18).";
RL Biochim. Biophys. Acta 393:379-382(1975).
RN [14]
RP VARIANT ROOSEVELT GLU-21.
RX PubMed=952968; DOI=10.1016/0005-2795(76)90089-1;
RA Rieder R.F., Clegg J.B., Weiss H.J., Christy N.P., Rabinowitz R.;
RT "Hemoglobin A2-Roosevelt: alpha 2 delta 2 20Val replaced by Glu.";
RL Biochim. Biophys. Acta 439:501-504(1976).
RN [15]
RP VARIANT CANADA ASN-100.
RX PubMed=7129931;
RA Salkie M.L., Gordon P.A., Rigal W.M., Lam H., Wilson J.B.,
RA Headlee M.E., Huisman T.H.J.;
RT "Hb A2-Canada or alpha 2 delta 2 99(G1) Asp replaced by Asn, a newly
RT discovered delta chain variant with increased oxygen affinity
RT occurring in cis to beta-thalassemia.";
RL Hemoglobin 6:223-231(1982).
RN [16]
RP VARIANT MANZANARES VAL-122.
RX PubMed=6629825;
RA Romero Garcia C., Navarro J.L., Lam H., Webber B.B., Headlee M.G.,
RA Wilson J.B., Huisman T.H.J.;
RT "Hb A2-Manzanares or alpha 2 delta 2 121 (GH4) Glu replaced by Val, an
RT unstable delta chain variant observed in a Spanish family.";
RL Hemoglobin 7:435-442(1983).
RN [17]
RP VARIANT ZAGREB GLU-126.
RX PubMed=6629826;
RA Juricic D., Crepinko I., Efremov G.D., Lam H., Webber B.B.,
RA Headlee M.G., Huisman T.H.J.;
RT "Hb A2-Zagreb or alpha 2 delta 2(125)(H3)Gln replaced by Glu, a new
RT delta chain variant in association with delta beta-thalassemia.";
RL Hemoglobin 7:443-448(1983).
RN [18]
RP VARIANT VICTORIA ASP-25.
RX PubMed=6469695;
RA Brennan S.O., Williamson D., Smith M.B., Cauchi M.N., Macphee A.,
RA Carrell R.W.;
RT "HbA2 Victoria delta 24 (B6) Gly-->Asp. A new delta chain variant
RT occurring with beta-thalassemia.";
RL Hemoglobin 8:163-168(1984).
RN [19]
RP VARIANT FITZROY ASP-143.
RX PubMed=6548205;
RA Williamson D., Brennan S.O., Strosberg H., Whitty J., Carrell R.W.;
RT "Hemoglobin A2 Fitzroy delta 142 Ala-->Asp: a new delta-chain
RT variant.";
RL Hemoglobin 8:325-332(1984).
RN [20]
RP VARIANT HONAI VAL-91.
RX PubMed=2869009;
RA Fujita S., Ohta Y., Saito S., Kobayashi Y., Naritomi Y., Kawaguchi T.,
RA Imamura T., Wada Y., Hayashi A.;
RT "Hemoglobin A2 Honai (alpha 2 delta 2(90)(F6)Glu-->Val): a new delta
RT chain variant.";
RL Hemoglobin 9:597-607(1985).
RN [21]
RP VARIANT YOKOSHIMA ASP-26.
RX PubMed=3841531;
RA Ohba Y., Igarashi M., Tsukahara M., Nakashima M., Sanada C., Ami M.,
RA Arai Y., Miyaji T.;
RT "Hb A2 Yokoshima, alpha(2)delta(2)25(B7)Gly-->Asp, a new delta chain
RT variant found in a Japanese family.";
RL Hemoglobin 9:613-615(1985).
RN [22]
RP VARIANT WRENS MET-99.
RX PubMed=2477064; DOI=10.1016/0167-4781(89)90083-3;
RA Codrington J.F., Kutlar F., Harris H.F., Wilson J.B., Stoming T.A.,
RA Huisman T.H.J.;
RT "Hb A2-Wrens or alpha 2 delta 2 98(FG5) Val-->Met, an unstable delta
RT chain variant identified by sequence analysis of amplified DNA.";
RL Biochim. Biophys. Acta 1009:87-89(1989).
RN [23]
RP VARIANTS YIALOUSA SER-28; CORFU CYS-117 AND PELENDRI PRO-142.
RX PubMed=1742490;
RA Trifillis P., Ioannou P., Schwartz E., Surrey S.;
RT "Identification of four novel delta-globin gene mutations in Greek
RT Cypriots using polymerase chain reaction and automated fluorescence-
RT based DNA sequence analysis.";
RL Blood 78:3298-3305(1991).
RN [24]
RP VARIANT NIIGATA ALA-2.
RX PubMed=1787103;
RA Harano T., Harano K., Kushida Y., Ueda S., Kawakami H.;
RT "Hb A2-Niigata [delta 1(NA1)Val-->Ala]: a new delta chain variant
RT found in the Japanese population.";
RL Hemoglobin 15:335-339(1991).
RN [25]
RP VARIANT PARKVILLE VAL-48.
RX PubMed=1802883;
RA Leung H., Gilbert A.T., Fleming P.J., Wong J., Hughes W.G.,
RA Hussein S., Nash A.R.;
RT "Hb A2-Parkville or delta 47(CD6)Asp-->Val, a new delta chain
RT variant.";
RL Hemoglobin 15:407-416(1991).
RN [26]
RP VARIANT CORFU CYS-117.
RX PubMed=2066116; DOI=10.1007/BF00204193;
RA Loudianos G., Murru S., Kanavakis E., Metaxotou-Mavromati A.,
RA Theodoropoulou D., Kattamis C., Cao A., Pirastu M.;
RT "A new delta chain variant hemoglobin A2-Corfu or alpha 2 delta 2 116
RT Arg-->Cys (G18), detected by delta-globin gene analysis in a Greek
RT family.";
RL Hum. Genet. 87:237-238(1991).
RN [27]
RP VARIANTS ILE-5 AND YIALOUSA SER-28.
RX PubMed=8364213;
RA Trifillis P., Kyrri A., Kalogirou E., Kokkofitou A., Ioannou P.,
RA Schwartz E., Surrey S.;
RT "Analysis of delta-globin gene mutations in Greek cypriots.";
RL Blood 82:1647-1651(1993).
RN [28]
RP VARIANT GROVETOWN VAL-76.
RX PubMed=8330984;
RA Molchanova T.P., Postnikov Y.V., Gu L.-H., Huisman T.H.J.;
RT "Hb A2-Grovetown or alpha 2 delta (2)75(E19)Leu-->Val.";
RL Hemoglobin 17:289-291(1993).
RN [29]
RP VARIANT PUGLIA ASP-27.
RX PubMed=8401543; DOI=10.1002/humu.1380020417;
RA Loudianos G., Porcu S., Cossu P., Tannoia N., Vitucci A.,
RA Campanale D., Cao A., Pirastu M.;
RT "A new delta-chain variant hemoglobin A2-Puglia or alpha 2 delta 2 26
RT Glu-->Asp (B8), detected by DNA analysis in a family of southern
RT Italian origin.";
RL Hum. Mutat. 2:327-329(1993).
RN [30]
RP VARIANT SANT' ANTIOCO GLY-94.
RX PubMed=7713748;
RA Galanello R., Gasperini D., Perseu L., Barella S., Ideo A., Cao A.;
RT "Hb A2-Sant' Antioco alpha 2 delta (2)93(F9)Cys-->Gly: a new delta
RT chain variant identified by sequencing of amplified DNA.";
RL Hemoglobin 18:437-439(1994).
RN [31]
RP VARIANT AGRINIO GLY-44.
RX PubMed=8537235;
RA Papadakis M., Drakoulakou O., Papapanagiotou E., Pessini D.,
RA Loutradi-Anagnostou A.;
RT "Hb A2-Agrinio [delta 43(CD2)Glu-->Gly(GAG-->GGG)]: a new delta chain
RT variant detected in a Greek family.";
RL Hemoglobin 19:295-299(1995).
RN [32]
RP VARIANTS PYLOS GLY-12 AND ETOLIA SER-86.
RX PubMed=9101295;
RX DOI=10.1002/(SICI)1098-1004(1997)9:4<344::AID-HUMU7>3.0.CO;2-5;
RA Drakoulakou O., Papapanagiotou E., Loutradi-Anagnostou A.,
RA Papadakis M.;
RT "Delta-thalassemic phenotype due to two 'novel' delta-globin gene
RT mutations: CD11[GTC-->GGC (A8)-HbA2-Pylos] and CD 85[TTT-->TCT(F1)-
RT HbA2-Etolia].";
RL Hum. Mutat. 9:344-347(1997).
RN [33]
RP VARIANT MONREALE ARG-147.
RX PubMed=11939506; DOI=10.1081/HEM-120002934;
RA De Angioletti M., Di Girgenti C., Messineo R., Capra M., Carestia C.;
RT "Hb A2-Monreale delta146(HC3)His-->Arg, a novel delta chain variant
RT detected in west Sicily.";
RL Hemoglobin 26:1-5(2002).
RN [34]
RP VARIANTS METAPONTO HIS-37; CAMPANIA LYS-58; LUCANIA VAL-89 AND CAPRI
RP SER-105.
RX PubMed=12402333; DOI=10.1002/humu.10132;
RA De Angioletti M., Lacerra G., Gaudiano C., Mastrolonardo G.,
RA Pagano L., Mastrullo L., Masciandaro S., Carestia C.;
RT "Epidemiology of the delta globin alleles in southern Italy shows
RT complex molecular, genetic, and phenotypic features.";
RL Hum. Mutat. 20:358-367(2002).
RN [35]
RP VARIANT NINIVE ALA-134.
RX PubMed=15921167; DOI=10.1081/HEM-200058593;
RA Frischknecht H., Dutly F.;
RT "Two new delta-globin mutations: Hb A2-Ninive [delta133(H11)Val-Ala]
RT and a delta(+)-thalassemia mutation [-31 (A-->G)] in the TATA box of
RT the delta-globin gene.";
RL Hemoglobin 29:151-154(2005).
RN [36]
RP VARIANT MUMC/CORLEONE ASP-11.
RX PubMed=16370490; DOI=10.1080/03630260500310794;
RA Walker L., Patterson M., Eng B., McFarlane A., Waye J.S.;
RT "Identification of a new delta chain hemoglobin variant in a beta-
RT thalassemia carrier: Hb A2-mumc [delta13(a10)Ala-->Asp].";
RL Hemoglobin 29:285-287(2005).
RN [37]
RP VARIANTS CATANIA LEU-3; MUMC/CORLEONE ASP-11; VENTIMIGLIA GLY-71;
RP MONTECHIARO LYS-88 AND BAGHERIA VAL-141.
RX PubMed=17145605;
RA Giambona A., Passarello C., Ruggeri G., Renda D., Teresi P., Anza M.,
RA Maggio A.;
RT "Analysis of delta-globin gene alleles in the Sicilian population:
RT identification of five new mutations.";
RL Haematologica 91:1681-1684(2006).
CC -!- FUNCTION: Involved in oxygen transport from the lung to the
CC various peripheral tissues.
CC -!- SUBUNIT: Heterotetramer of two alpha chains and two delta chains
CC in adult hemoglobin A2 (HbA2). HbA2 represents less than 3.5% of
CC adult hemoglobin.
CC -!- TISSUE SPECIFICITY: Red blood cells.
CC -!- SIMILARITY: Belongs to the globin family.
CC -!- WEB RESOURCE: Name=HbVar; Note=Human hemoglobin variants and
CC thalassemias;
CC URL="http://globin.bx.psu.edu/cgi-bin/hbvar/query_vars3?mode=directlink&gene;=HBD";
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DR EMBL; U01317; AAA16333.1; -; Genomic_DNA.
DR EMBL; V00505; CAA23763.1; -; Genomic_DNA.
DR EMBL; AF339401; AAL72102.1; -; Genomic_DNA.
DR EMBL; AF339402; AAL72103.1; -; Genomic_DNA.
DR EMBL; AF339403; AAL72104.1; -; Genomic_DNA.
DR EMBL; AF339404; AAL72105.1; -; Genomic_DNA.
DR EMBL; AF339405; AAL72106.1; -; Genomic_DNA.
DR EMBL; AF339406; AAL72107.1; -; Genomic_DNA.
DR EMBL; AF339407; AAL72108.1; -; Genomic_DNA.
DR EMBL; AF339408; AAL72109.1; -; Genomic_DNA.
DR EMBL; AF339409; AAL72110.1; -; Genomic_DNA.
DR EMBL; AF339410; AAL72111.1; -; Genomic_DNA.
DR EMBL; AF339411; AAL72112.1; -; Genomic_DNA.
DR EMBL; AF339412; AAL72113.1; -; Genomic_DNA.
DR EMBL; AF339413; AAL72114.1; -; Genomic_DNA.
DR EMBL; AF339414; AAL72115.1; -; Genomic_DNA.
DR EMBL; AF339415; AAL72116.1; -; Genomic_DNA.
DR EMBL; AF339416; AAL72117.1; -; Genomic_DNA.
DR EMBL; AF339417; AAL72118.1; -; Genomic_DNA.
DR EMBL; AY034468; AAK68847.1; -; mRNA.
DR EMBL; DQ157442; AAZ83699.1; -; Genomic_DNA.
DR EMBL; BC069307; AAH69307.1; -; mRNA.
DR EMBL; BC070282; AAH70282.1; -; mRNA.
DR PIR; A90804; HDHU.
DR RefSeq; NP_000510.1; NM_000519.3.
DR UniGene; Hs.699280; -.
DR PDB; 1SHR; X-ray; 1.88 A; B/D=2-146.
DR PDB; 1SI4; X-ray; 2.20 A; B/D=2-146.
DR PDBsum; 1SHR; -.
DR PDBsum; 1SI4; -.
DR ProteinModelPortal; P02042; -.
DR SMR; P02042; 2-147.
DR IntAct; P02042; 1.
DR STRING; 9606.ENSP00000369654; -.
DR PhosphoSite; P02042; -.
DR DMDM; 122713; -.
DR REPRODUCTION-2DPAGE; IPI00473011; -.
DR UCD-2DPAGE; P02042; -.
DR PaxDb; P02042; -.
DR PeptideAtlas; P02042; -.
DR PRIDE; P02042; -.
DR DNASU; 3045; -.
DR Ensembl; ENST00000380299; ENSP00000369654; ENSG00000223609.
DR GeneID; 3045; -.
DR KEGG; hsa:3045; -.
DR UCSC; uc001maf.1; human.
DR CTD; 3045; -.
DR GeneCards; GC11M005253; -.
DR HGNC; HGNC:4829; HBD.
DR HPA; CAB037087; -.
DR MIM; 142000; gene.
DR neXtProt; NX_P02042; -.
DR Orphanet; 231237; Delta-beta thalassemia.
DR Orphanet; 330032; Hemoglobin Lepore - beta-thalassemia.
DR PharmGKB; PA29204; -.
DR eggNOG; NOG269316; -.
DR HOGENOM; HOG000036868; -.
DR HOVERGEN; HBG009709; -.
DR InParanoid; P02042; -.
DR KO; K16151; -.
DR OMA; CASAIMG; -.
DR Reactome; REACT_604; Hemostasis.
DR ChiTaRS; HBD; human.
DR EvolutionaryTrace; P02042; -.
DR GeneWiki; HBD; -.
DR GenomeRNAi; 3045; -.
DR NextBio; 12055; -.
DR PRO; PR:P02042; -.
DR ArrayExpress; P02042; -.
DR Bgee; P02042; -.
DR CleanEx; HS_HBD; -.
DR Genevestigator; P02042; -.
DR GO; GO:0005833; C:hemoglobin complex; TAS:ProtInc.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0019825; F:oxygen binding; IEA:InterPro.
DR GO; GO:0005344; F:oxygen transporter activity; IEA:UniProtKB-KW.
DR GO; GO:0007596; P:blood coagulation; TAS:Reactome.
DR Gene3D; 1.10.490.10; -; 1.
DR InterPro; IPR000971; Globin.
DR InterPro; IPR009050; Globin-like.
DR InterPro; IPR012292; Globin_dom.
DR InterPro; IPR002337; Haemoglobin_b.
DR Pfam; PF00042; Globin; 1.
DR PRINTS; PR00814; BETAHAEM.
DR SUPFAM; SSF46458; SSF46458; 1.
DR PROSITE; PS01033; GLOBIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Complete proteome;
KW Direct protein sequencing; Heme; Iron; Metal-binding;
KW Oxygen transport; Polymorphism; Reference proteome; Transport.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 147 Hemoglobin subunit delta.
FT /FTId=PRO_0000053167.
FT METAL 64 64 Iron (heme distal ligand).
FT METAL 93 93 Iron (heme proximal ligand).
FT MOD_RES 2 2 N-acetylalanine; in variant Niigata.
FT VARIANT 2 2 V -> A (in Niigata; dbSNP:rs34991152).
FT /FTId=VAR_003096.
FT VARIANT 3 3 H -> L (in Catania).
FT /FTId=VAR_030499.
FT VARIANT 3 3 H -> R (in Sphakia; dbSNP:rs35433207).
FT /FTId=VAR_003097.
FT VARIANT 5 5 T -> I (in dbSNP:rs35406175).
FT /FTId=VAR_018740.
FT VARIANT 5 5 T -> S (in haplotype T11; Kenya;
FT dbSNP:rs35406175).
FT /FTId=VAR_018741.
FT VARIANT 11 11 A -> D (in MUMC/Corleone).
FT /FTId=VAR_030500.
FT VARIANT 12 12 V -> G (in Pylos; dbSNP:rs34090605).
FT /FTId=VAR_030501.
FT VARIANT 13 13 N -> K (in NYU; dbSNP:rs34313675).
FT /FTId=VAR_003098.
FT VARIANT 17 17 G -> R (in Delta'; dbSNP:rs34012192).
FT /FTId=VAR_003099.
FT VARIANT 21 21 V -> E (in Roosevelt; dbSNP:rs34093840).
FT /FTId=VAR_003100.
FT VARIANT 23 23 A -> E (in Flatbush; dbSNP:rs35395083).
FT /FTId=VAR_003101.
FT VARIANT 25 25 G -> D (in Victoria; dbSNP:rs34460332).
FT /FTId=VAR_003102.
FT VARIANT 26 26 G -> D (in Yokoshima; dbSNP:rs34389944).
FT /FTId=VAR_003103.
FT VARIANT 27 27 E -> D (in Puglia; dbSNP:rs34289459).
FT /FTId=VAR_003104.
FT VARIANT 28 28 A -> S (in Yialousa; dbSNP:rs35152987).
FT /FTId=VAR_003105.
FT VARIANT 37 37 P -> H (in Metaponto; dbSNP:rs34383555).
FT /FTId=VAR_030502.
FT VARIANT 44 44 E -> G (in Agrinio; dbSNP:rs36084266).
FT /FTId=VAR_003106.
FT VARIANT 44 44 E -> K (in Melbourne; dbSNP:rs35166721).
FT /FTId=VAR_003107.
FT VARIANT 48 48 D -> V (in Parkville; dbSNP:rs34977235).
FT /FTId=VAR_003108.
FT VARIANT 52 52 P -> R (in Adria; dbSNP:rs34489183).
FT /FTId=VAR_003109.
FT VARIANT 58 58 N -> K (in Campania; dbSNP:rs35666685).
FT /FTId=VAR_030503.
FT VARIANT 70 70 G -> R (in Indonesia; dbSNP:rs35913713).
FT /FTId=VAR_003110.
FT VARIANT 71 71 A -> G (in Ventimiglia).
FT /FTId=VAR_030504.
FT VARIANT 76 76 L -> V (in Grovetown; dbSNP:rs34430836).
FT /FTId=VAR_003111.
FT VARIANT 86 86 F -> S (in Etolia; dbSNP:rs35633566).
FT /FTId=VAR_030505.
FT VARIANT 88 88 Q -> K (in Montechiaro).
FT /FTId=VAR_030506.
FT VARIANT 89 89 L -> V (in Lucania; dbSNP:rs34933313).
FT /FTId=VAR_030507.
FT VARIANT 91 91 E -> V (in Honai; dbSNP:rs34420481).
FT /FTId=VAR_003112.
FT VARIANT 94 94 C -> G (in Sant' Antioco;
FT dbSNP:rs28933077).
FT /FTId=VAR_014277.
FT VARIANT 99 99 V -> M (in Wrens; unstable;
FT dbSNP:rs28933076).
FT /FTId=VAR_003113.
FT VARIANT 100 100 D -> N (in Canada; O(2) affinity up;
FT dbSNP:rs35329985).
FT /FTId=VAR_003114.
FT VARIANT 105 105 R -> S (in Capri; dbSNP:rs34390965).
FT /FTId=VAR_030508.
FT VARIANT 117 117 R -> C (in Corfu/Troodos;
FT dbSNP:rs33971270).
FT /FTId=VAR_003115.
FT VARIANT 117 117 R -> H (in Coburg; dbSNP:rs34536353).
FT /FTId=VAR_003116.
FT VARIANT 118 118 N -> D (in LiangCheng; dbSNP:rs36049174).
FT /FTId=VAR_003117.
FT VARIANT 122 122 E -> V (in Manzanares; unstable;
FT dbSNP:rs35790721).
FT /FTId=VAR_003118.
FT VARIANT 126 126 Q -> E (in Zagreb; dbSNP:rs36078803).
FT /FTId=VAR_003119.
FT VARIANT 134 134 V -> A (in Ninive).
FT /FTId=VAR_030509.
FT VARIANT 137 137 G -> D (in Babinga; dbSNP:rs35849348).
FT /FTId=VAR_003120.
FT VARIANT 141 141 A -> V (in Bagheria).
FT /FTId=VAR_030510.
FT VARIANT 142 142 L -> P (in Pelendri).
FT /FTId=VAR_003121.
FT VARIANT 143 143 A -> D (in Fitzroy).
FT /FTId=VAR_003122.
FT VARIANT 147 147 H -> R (in Monreale).
FT /FTId=VAR_014278.
FT HELIX 6 16
FT TURN 21 23
FT HELIX 24 35
FT HELIX 37 46
FT HELIX 52 56
FT HELIX 59 77
FT TURN 78 80
FT HELIX 82 85
FT HELIX 87 94
FT HELIX 102 119
FT HELIX 120 122
FT HELIX 125 142
FT HELIX 144 146
SQ SEQUENCE 147 AA; 16055 MW; F86BA4A09A57BB05 CRC64;
MVHLTPEEKT AVNALWGKVN VDAVGGEALG RLLVVYPWTQ RFFESFGDLS SPDAVMGNPK
VKAHGKKVLG AFSDGLAHLD NLKGTFSQLS ELHCDKLHVD PENFRLLGNV LVCVLARNFG
KEFTPQMQAA YQKVVAGVAN ALAHKYH
//

MIM 142000
*RECORD*
*FIELD* NO
142000
*FIELD* TI
*142000 HEMOGLOBIN--DELTA LOCUS; HBD
*FIELD* TX
The delta locus determines the delta, or nonalpha, chain of hemoglobin
read moreA(2) (alpha-2/delta-2). Jeffreys (1979) found an example of a
restriction enzyme variant in a DNA intervening sequence of the
delta-globin gene. Spritz et al. (1980) could not 'identify
unambiguously the structural basis of the low level of expression
characteristic of the delta-globin gene.' They discussed the basis for
evolution of duplicate adult beta-type genes. Petes (1982) suggested
that some of the structural variants of the delta chain may be the
consequence of a nonreciprocal transfer of information from the
beta-globin gene to the delta-globin gene by a process termed
'intrachromosomal gene conversion' (Klein and Petes, 1981). Losekoot et
al. (1989) described a patient who was a compound heterozygote for
delta-0-thalassemia and for a deletion type of thalassemia. By
amplifying the delta gene by PCR and sequencing it, they showed that the
mutant gene had an insertion of an extra nucleotide at the third
position of codon 91 of the second exon which gave rise to a premature
stop codon at position 94. They presented a model to explain the
insertion, namely, the formation of a hairpin loop by quasipalindromic
sequences.

Carver and Kutlar (1995) listed 27 delta-chain variants as of the
beginning of 1995.

The first-to-be discovered fusion hemoglobin, hemoglobin Lepore (which
has several forms) has HBD sequence at the 5-prime end and HBB (141900)
sequence at the 3-prime end. See, for example, Hb Lepore (Baltimore)
(142000.0019) and Hb Lepore (Boston) (142000.0020). Formed by
nonhomologous pairing and unequal crossing over, the fusion protein
resulting from the complementary event is referred to as Hb anti-Lepore
and has HBB sequence at the 5-prime end and HBD sequence at the 3-prime
end; see, for example, hemoglobin Lincoln Park (141900.0157). Carver and
Kutlar (1995) listed 10 fusion hemoglobins that had been described by
the beginning of 1995.

De Angioletti et al. (2002) characterized mutations and haplotypes of
the HBD gene in 2 regions of southern Italy. They screened approximately
10,000 students in Basilicata and found 53 carriers of HBD variants in
43 unrelated families; in Campania, patients were ascertained through a
routine thalassemia counseling service. They found 6 novel mutations and
stated that 46 HBD mutations had been previously characterized, of which
30 were from the Mediterranean area (Huisman and Carver, 1998).

*FIELD* AV
.0001
HEMOGLOBIN A(2)-PRIME
HEMOGLOBIN B(2)
HBD, GLY16ARG

See Horton et al. (1961), Ball et al. (1966), Vella and Graham (1969),
and Lehmann et al. (1985). Schiliro et al. (1991) found this variant,
which had previously been described almost exclusively in populations of
African origin, in 5 members of 2 unrelated families in Sicily. This was
taken as further evidence of the genetic admixture between African and
Sicilian populations.

Hb A(2)-prime is characterized by substitution of a glycine by an
arginine residue at position 16. Horton et al. (1961) found the carrier
frequency of the variant to be 1% to 3% in the black population of the
southeastern United States and Jenkins and Dunn (1981) found a frequency
of up to 9% in South African blacks. It occurs in about 9.2% in the
Herero population belonging to the South African Bantu-speaking blacks
from Namibia (Spurdle et al., 1994). In an epidemiologic study of
hemoglobin variants in the Dogon country of Mali, Bennani et al. (2003)
identified this Hb A(2) variant and characterized the associated
haplotype of the beta-globin gene cluster. In all cases it was linked to
a unique haplotype which was the same as that linked to Hb A(2)-prime in
the Herero population. Although the unique origin of this mutation in
Africa was considered a possibility, a recurrent mutational event could
not be excluded because the linked beta-cluster haplotype was 1 of the 2
major haplotypes found in all African populations.

Jones et al. (1967) found this mutation in compound heterozygous state
with hemoglobin A(2) Flatbush (142000.0007).

.0002
HEMOGLOBIN A(2) ADRIA
HBD, PRO51ARG

XIII Meeting Gruppo di Studio Dell 'Entrocita': Torino, 12 June, 1977.

.0003
HEMOGLOBIN A(2) BABINGA
HBD, GLY136ASP

See De Jong and Bernini (1968).

.0004
HEMOGLOBIN A(2) CANADA
HBD, ASP99ASN

In an Asiatic Indian family, Salkie et al. (1982) observed a delta
variant hemoglobin with increased oxygen affinity. Asparagine was
substituted for aspartic acid at delta 99. The same substitution occurs
in the beta chain in Hb Kempsey, which, like other substitutions at beta
99, is accompanied by erythrocytosis due to its increased oxygen
affinity.

.0005
HEMOGLOBIN A(2) COBURG
HBD, ARG116HIS

See Sharma et al. (1975).

.0006
HEMOGLOBIN A(2) FITZROY
HBD, ALA142ASP

See Williamson et al. (1984).

.0007
HEMOGLOBIN A(2) FLATBUSH
HEMOGLOBIN FLATBUSH (GEORGIA)
HBD, ALA22GLU

See Lee and Huisman (1964) and Jones et al. (1967).

.0008
HEMOGLOBIN A(2) HONAI
HBD, GLU90VAL

See Fujita et al. (1985).

.0009
HEMOGLOBIN A(2) INDONESIA
HBD, GLY69ARG

See Lie-Injo et al. (1971).

.0010
HEMOGLOBIN A(2) MANZANARES
HBD, GLU121VAL

See Romero Garcia et al. (1983).

.0011
HEMOGLOBIN A(2) MELBOURNE
HBD, GLU43LYS

See Sharma et al. (1974).

.0012
HEMOGLOBIN A(2) NYU
HEMOGLOBIN NYU
HBD, ASN12LYS

See Ranney et al. (1969) and De Jong and Went (1974). Schiliro et al.
(1991) found this rare variant in 2 members of a family in Sicily. They
interpreted their findings of 6 rare hemoglobin variants in Sicily as
reflecting the fact that Sicily was at the crossroads of the world for
thousands of years.

De Angioletti et al. (2002) found this variant in 11 families from
Basilicata, southern Italy, associated with haplotype I. Because all 11
families lived in a restricted area extending from the Ionian coast for
15 kilometers along the Angri and Sinni Rivers, De Angioletti et al.
(2002) suggested a founder effect.

.0013
HEMOGLOBIN A(2) ROOSEVELT
HBD, VAL20GLU

See Rieder et al. (1976).

.0014
HEMOGLOBIN A(2) SPHAKIA
HBD, HIS2ARG

See Jones et al. (1966).

.0015
HEMOGLOBIN A(2) VICTORIA
HBD, GLY24ASP

See Brennan et al. (1984).

.0016
HEMOGLOBIN A(2) WRENS
HBD, VAL98MET

Substitution of methionine for valine as amino acid 98 in the delta
chain of hemoglobin A(2) was found by Codrington et al. (1989) when they
studied an 85-year-old black male who had an allele for hereditary
persistence of fetal hemoglobin on 1 chromosome and a suspected
'delta-thalassemia' on the other. Sequence analysis of amplified DNA
showed the GTG-to-ATG mutation of codon 98. Thus, the delta-thalassemia
was caused by the presence of a Hb A(2) variant that was unstable to an
extent similar to Hb Koln, its beta-chain counterpart. The proband had a
very low level of hemoglobin A(2).

.0017
HEMOGLOBIN A(2) YOKOSHIMA
HBD, GLY25ASP

See Ohba et al. (1985).

.0018
HEMOGLOBIN A(2) ZAGREB
HBD, GLN125GLU

See Juricic et al. (1983).

.0019
HEMOGLOBIN LEPORE (BALTIMORE)
HBD50/HBB86 FUSION

Delta-beta fusion (delta 50 to beta 86) is the molecular lesion. See
Ostertag and Smith (1969) and Efremov et al. (1976). Among 5 chromosomes
carrying the Hb Lepore (Baltimore) hybrid gene, Lanclos et al. (1987)
found a characteristic haplotype.

.0020
HEMOGLOBIN LEPORE (BOSTON)
HEMOGLOBIN LEPORE (WASHINGTON);;
HEMOGLOBIN LEPORE (AUGUSTA);;
HEMOGLOBIN PYLOS
HBD87/HBB116 FUSION

Delta-beta fusion (delta 87 to beta 116) is the molecular lesion.
Different hemoglobins Lepore show evidence that the crossover occurred
at different sites: e.g., Hb Lepore (Washington) has the shift-over
somewhere between amino acids at 87 and 116 (Labie et al., 1966). (It is
impossible to position it more precisely because the delta and beta
chains are identical between these residues.) Among 44 chromosomes
carrying the Hb Lepore (Washington) hybrid gene, Lanclos et al. (1987)
found 2 and possibly 3 different haplotypes. See Baglioni (1962), Fessas
et al. (1962), Curtain (1964), and Ahern et al. (1972). Using maternal
blood as a source for fetal cells in 3 pregnancies at risk for
beta-thalassemia/hemoglobin Lepore disease, Camaschella et al. (1990)
made a molecular diagnosis of hemoglobin Lepore-Boston in the fetus.
Taking advantage of the PCR method for amplifying Lepore-specific DNA
fragments in families in which Hb Lepore was inherited on the paternal
side, they demonstrated in 2 cases and excluded in 1 the presence of
this hemoglobinopathy in the fetus through the study of DNA from the
maternal blood. This is one of the first instances of prenatal diagnosis
by study of fetal cells in the maternal circulation. Fioretti et al.
(1992) identified a hybrid delta-beta-globin gene in 40 families living
in Abruzzo and Campania, which are on the east and west coast of Italy,
respectively. In all cases the gene was of the Lepore-Boston type: it
had the delta-globin sequence up to exon 2 codon 87 and had the
beta-globin sequence from nucleotide 8 of IVS2. Between these 2 ends,
the gene had 58 bp in common with the delta- and beta-globin genes.
Fioretti et al. (1992) found that 12 of 12 genes from Abruzzo were of 1
haplotype, which was present in only 8 of 31 genes from Campania. The
other Campania genes were all of another haplotype. DNA sequencing of
homozygous subjects who showed the 'Abruzzo haplotype' had G at
nucleotide 74 of IVS2, whereas those of the alternative haplotype had a
T at that site. The geographic pattern as well as the molecular
characteristics suggested to Fioretti et al. (1992) that Hb
Lepore-Boston had had recurrent and multicentric origins.

.0021
HEMOGLOBIN LEPORE (HOLLANDIA)
HBD22/HBB50 FUSION

Delta-beta fusion (delta 22 to beta 50) is the molecular lesion. Several
hemoglobins Lepore have been shown to differ in the position of the
crossover between the delta and beta chains (Curtain, 1964). See Neeb et
al. (1961), Barnabas and Muller (1962), and Baglioni (1962).

Edison et al. (2005) discussed the clinical picture resulting from
heterozygosity for hemoglobin E beta-thalassemia (141900.0071) and Hb
Lepore (Hollandia) on the basis of a case in India.

.0022
HEMOGLOBIN PARCHMAN
HBD1-12/HBB22-50/HBD87-146 FUSION

A delta-beta-delta hybrid nonalpha globin chain, presumably the result
of a double crossover in the nonalpha-globin region, is the molecular
lesion. One crossover apparently occurred between the codons for
residues 12 and 22 and the second between the codons for residues 50 and
86 of the beta globin chain. See Adams et al. (1981, 1982).

.0023
DELTA-ZERO-THALASSEMIA, KNOSSOS TYPE
HBD, 1-BP DEL, AAG59AG, FS60TER

Hb Knossos (HBB, ala27-to-ser, 141900.0149) is a silent beta-plus
thalassemia variant, which was first described in a Greek family.
Heterozygotes from the Mediterranean area show low Hb A2 levels and
homozygotes show absence of Hb A2. In contrast, heterozygotes in a
family from the French West Indies had high Hb A2 levels typical of
classic beta-thalassemia carriers. Loudianos et al. (1991) found a
single nucleotide deletion at codon 59 (AAG to AG) of the HBD gene,
producing a frameshift which resulted in the production of a stop codon
at position 60.

.0024
HEMOGLOBIN A(2) CORFU
HEMOGLOBIN A(2) TROODOS
HBD, ARG116CYS

Loudianos et al. (1991) found a C-to-T mutation resulting in
substitution of cysteine (TGC) for arginine (CGC) at position 116 of the
delta chain. Hb A2-Coburg (142000.0005) has mutation at the same
nucleotide. In a study of a Greek Cypriot family suspected of having
delta-thalassemia, Trifillis et al. (1991) found this same mutation.

.0025
HEMOGLOBIN A(2) PARKVILLE
HBD, ASP47VAL

In a female of Italian parentage living in Australia, Leung et al.
(1991) described a substitution of aspartic acid-47 by valine in the
delta-globin chain.

.0026
DELTA-THALASSEMIA
HBD, G-A, +69

Oggiano et al. (1987) described a family of northern Sardinian descent
in which the propositus was affected by thalassemia major, resulting
from compound heterozygosity for the codon 39 missense mutation and the
beta+ IVS2 nucleotide 745 mutation, and in which all heterozygotes for
the latter mutation had normal HbA-2 levels. Moi et al. (1992) found
that the delta-thalassemia gene in cis to the latter mutation showed a
G-to-A change 69 nucleotides downstream to the poly(A) addition site.
The normal G at position 69 is part of a GATA box that is a binding site
for the GATA-1 protein. A DNA fragment containing the GATA motif with
the G-to-A substitution at position +69 had increased binding affinity
for erythroid-specific DNA binding protein(s) as compared with the
wildtype sequence.

.0027
HEMOGLOBIN A(2) NIIGATA
HBD, VAL1ALA

See Harano et al. (1991).

.0028
DELTA-THALASSEMIA
HEMOGLOBIN A(2) YIALOUSA
HBD, ALA27SER

Renda et al. (1992) demonstrated homozygosity for a G-to-T transversion
at the first nucleotide of codon 27 of the delta-globin gene in a
Sicilian woman. This mutation had first been demonstrated in Sardinia by
Moi et al. (1988). In an attempt to identify mutations that might be the
basis of delta-thalassemia, Trifillis et al. (1991) amplified by PCR the
HBD region from 3 Greek Cypriot families and determined the DNA
sequence. Four novel mutations were identified. One of these was a
G-to-T transversion at codon 27 resulting in an alanine to serine
change. The G-to-T change presumably activates a cryptic splice site
resulting in aberrant transcript processing.

De Angioletti et al. (2002) found this variant in 42 of 63 families in 2
regions of southern Italy.

.0029
DELTA-THALASSEMIA
HBD, ARG30THR

Loudianos et al. (1992) found that an individual of southern Italian
descent was heterozygous for Sicilian delta-beta-thalassemia and for
delta-thalassemia. Direct sequencing of the amplified delta-globin gene
demonstrated that the allele responsible for delta-thalassemia carried a
G-to-C substitution of the last nucleotide of exon 1 which most likely
adversely affected pre-mRNA splicing. An identical G-to-C mutation
predicting substitution of threonine for arginine at codon 30 has been
identified in the beta-globin chain, where it results in
beta-thalassemia because of a marked (98%) reduction of mRNA splicing at
the 5-prime splice site of IVS1 of the beta-globin gene (141900.0144).
Loudianos et al. (1992) cited 2 other examples of identical mutations
observed in the beta- and delta-globin genes. They suggested that such
might occur in these 2 linked genes either as independent mutations or
as the result of gene conversion events.

.0030
DELTA-THALASSEMIA
HBD, T-C, -77

In 3 unrelated Japanese patients homozygous for delta-thalassemia,
Matsuda et al. (1992) detected a T-to-C substitution at position -77 of
the HBD gene. The mutation is located within the inverted binding motif
of GATA-1 (305371), an erythroid cell-specific transcription factor.
They found that GATA-1 did not bind to an oligonucleotide with the
mutation at position -77.

.0031
HEMOGLOBIN A(2) PELENDRI
HBD, LEU141PRO

In a Greek Cypriot family suspected of having delta-thalassemia,
Trifillis et al. (1991) found a T-to-C transition at codon 141
converting leucine to proline.

.0032
DELTA-THALASSEMIA
HBD, IVS2AS, A-G, -2

In a Greek Cypriot family with delta-thalassemia, Trifillis et al.
(1991) found a change from AG to GG in the last 2 nucleotides of the
3-prime acceptor site of IVS-2 of the HBD gene. The change resulted in
total absence of hemoglobin Hb A2. The same change in the beta-globin
gene results in a beta-0-thalassemia phenotype.

.0033
DELTA-THALASSEMIA
HEMOGLOBIN A(2) GROVETOWN
HBD, LEU75VAL

Delta-chain abnormal hemoglobins with neutral substitutions are
difficult to detect unless the amino acid replacement causes the variant
to have some special properties, such as Hb A(2) Niigata (142000.0027),
which is acetylated, or Hb A(2) Wrens (142000.0016), which is unstable.
Molchanova et al. (1993) discovered Hb A(2) Grovetown accidentally
during the course of a testing program for sickle cell anemia using
isoelectric focusing (IEF). The change was found to be a C-to-G mutation
converting codon 75 from CTG (leu) to GTG (val).

.0034
HEMOGLOBIN A(2) PUGLIA
HBD, GLU26ASP

In a southern Italian family in which the propositus has a
thalassemia-like hematologic disorder, Loudianos et al. (1993) found a
variant of hemoglobin A(2) in combination with heterozygous
beta-thalassemia. The variant, named Hb-Puglia after the birthplace of
the propositus, was found to be due to a G-to-C transversion at the
third position of codon 26 of the HBD gene, resulting in substitution of
aspartic acid for glutamic acid. In spite of the lack of modification in
the charge of the molecule resulting from the substitution, the variant
was resolved from the normal Hb A(2) by both cellulose acetate
electrophoresis and isoelectric focusing.

.0035
DELTA-0-THALASSEMIA
HBD, TRP37TER

In 3 subjects from the same Italian family, Gasperini et al. (1994)
described a G-to-A transition in codon 37 of the HBD gene, resulting in
the production of an 'in phase' termination codon: (TGG) trp to (TAG)
stop. The subjects with this change showed normal red cell indices and
low hemoglobin A2. Gasperini et al. (1994) indicated that this was the
first nonsense mutation identified in the delta-globin gene.
Characterization of the lesion should be an aid in identification of
double heterozygotes for delta- and beta-thalassemia who, because of
normal Hb A2 levels, may be missed in carrier screening programs for
beta-thalassemia.

.0036
HEMOGLOBIN A(2) SANT' ANTIOCO
HBD, CYS93GLY

During a beta-thalassemia screening program in Sardinia, Galanello et
al. (1994) found a variant Hb A(2) due to a TGT-to-GGT transversion that
changed codon 93 from cysteine to glycine.

.0037
HEMOGLOBIN A(2) AGRINIO
HBD, GLU43GLY

In a Greek family, Papadakis et al. (1995) found a new delta-chain
variant, producing altered electrophoretic mobility of hemoglobin A(2).
Direct sequencing of amplified DNA revealed a change in codon 43 from
GAG (glu) to GGG (gly).

.0038
HEMOGLOBIN A(2) MONREALE
HBD, HIS146ARG

In a family from west Sicily, De Angioletti et al. (2002) detected an
abnormal hemoglobin by cation exchange high performance liquid
chromatography. The mutation was a substitution of CAT (his) by CGT
(arg) at codon 146 of the HBD gene. Two carriers had reduced levels of
normal hemoglobin A2 but comparable levels of the hemoglobin A2 variant.
The new variant was thought to have the same characteristics as Hb
Cochin-Port Royal which is the same mutation at the same position in the
HBB gene, his146 to arg (141900.0051); that variant is stable but has a
75% reduction of the Bohr effect.

.0039
HEMOGLOBIN A(2) METAPONTO
HBD, PRO37HIS

In 1 family from the Basilicata region of southern Italy, De Angioletti
et al. (2002) found a C-to-A transversion at position 238 of the HBD
genomic DNA that resulted in a pro37-to-his (P37H) substitution.
Hemoglobin A2 was 1.3% in the carrier, and mutant hemoglobin A2 was
0.6%, approximately 50% of the expected value.

.0040
HEMOGLOBIN A(2) CAMPANIA
HBD, ASN58LYS

In 1 family form the Campania region of southern Italy, De Angioletti et
al. (2002) found a C-to-A transversion at position 302 of the HBD
genomic DNA that resulted in an asn58-to-lys (N58K) substitution. Mutant
hemoglobin A2 was extremely low in the 2 carriers, corresponding to
approximately 15% of the total hemoglobin A2.

.0041
HEMOGLOBIN A(2) LUCANIA
HBD, LEU89VAL

In a family from the Basilicata region of southern Italy, De Angioletti
et al. (2002) found a C-to-G transversion at position 393 of the HBD
genomic DNA that resulted in a leu89-to-val (L89V) substitution. This
mutation appeared to have arisen in the carrier, as the parents did not
present the allele, paternity having been established by HLA typing and
RFLP haplotypes.

.0042
HEMOGLOBIN A(2) CAPRI
HBD, ARG105SER

In 1 family from the Campania region of southern Italy, De Angioletti et
al. (2002) found a G-to-T transversion at position 443 of the HBD
genomic DNA that resulted in an arg-to-ser change at codon 105 (R105S).

.0043
DELTA-THALASSEMIA
HBD, IVS2, T-A, +6

In 1 family frpm the Basilicata region of southern Italy, De Angioletti
et al. (2002) found a T-to-A transversion at position 6 of the consensus
sequence of the donor site of intron 2 of the HBD gene. The 2 carriers
showed mild Hb A2 decrease with normal iron metabolism. Hb A2 values
indicated that the mutation most likely affects splicing efficiency of
intron 2.

.0044
DELTA-THALASSEMIA
HBD, -126A-T

In 1 family from the Campania region of southern Italy, De Angioletti et
al. (2002) found an A-to-T transversion at position -126 of the HBD
gene. This mutation was located within the GATA motif and was thought to
abolish GATA1 binding and lead to a null allele.

.0045
HEMOGLOBIN A(2) NINIVE
HBD, VAL133ALA

In a 2-year-old girl originally from Ninive, Iraq, who presented with
microcytic anemia and minimal growth retardation, Frischknecht and Dutly
(2005) identified heterozygosity for a GTG-to-GCG transition at codon
133 of the HBD gene. This HBD mutation is analogous to the beta-chain
mutation Hb Renert (val133 to ala; 141900.0496).

.0046
DELTA-PLUS-THALASSEMIA
HBD, -31A-G

In a 40-year-old Italian with typical but mild thalassemic hematologic
indices, Frischknecht and Dutly (2005) found double heterozygosity for 2
thalassemia mutations. One was the common IVS1+6 (T-to-C) of the HBB
gene (141900.0360); the other was a -31A-G transition within the TATA
box of the HBD gene. This mutation is analogous to the -31A-G mutation
in the HBB gene (141900.0376). Simultaneous heterozygosity for
beta-thalassemia and delta-thalassemia is a frequent and well-known
complication in beta-thal carrier detection (see epidemiologic studies
in southern Italy by De Angioletti et al. (2002) that showed a wide
variety of HBD gene mutations that came to light because of their
association with HBB mutations in cases of beta-thalassemia).

.9999
HEMOGLOBIN DELTA VARIANTS, MOLECULAR DEFECT UNKNOWN

HEMOGLOBIN DELTA CHAIN TETRAMER. Not yet proven to be a tetramer. See
Huehns (1962) and Huehns et al. (1962).

HEMOGLOBIN LEPORE (CYPRUS). Delta-beta fusion. See Beaven et al. (1964).

HEMOGLOBIN LEPORE (THE BRONX). Delta-beta fusion. The N-terminal portion
is coded by a 5-prime part of the delta gene and the C-terminal portion
by a 3-prime part of the beta gene. See Ranney and Jacobs (1964) and
Ramirez et al. (1979).

*FIELD* SA
Baglioni and Ventruto (1968); Efremov (1978); Gerald and Diamond
(1958); Huisman and Sydenstricker (1962); Martin et al. (1980); Wilson
et al. (1981)
*FIELD* RF
1. Adams, J. G., III; Morrison, W. T.; Steinberg, M. H.: A double
crossover within a single human gene: Hb Parchman (NH-2-delta-beta-delta-COOH).
(Abstract) Am. J. Hum. Genet. 33: 34A only, 1981.

2. Adams, J. G., III; Morrison, W. T.; Steinberg, M. H.: Hemoglobin
Parchman: double crossover within a single human gene. Science 218:
291-293, 1982.

3. Ahern, E. J.; Ahern, V. N.; Aarons, G. H.; Jones, R. T.; Brimhall,
B.: Hemoglobin Lepore Washington in two Jamaican families: interaction
with beta chain variants. Blood 40: 246-256, 1972.

4. Baglioni, C.: The fusion of two peptide chains in hemoglobin Lepore
and its interpretation as a genetic deletion. Proc. Nat. Acad. Sci. 48:
1880-1886, 1962.

5. Baglioni, C.; Ventruto, V.: Human abnormal hemoglobins. II. A
chemical study of hemoglobin Lepore from a homozygote individual. Europ.
J. Biochem. 5: 29-32, 1968.

6. Ball, E. W.; Meynell, M. J.; Beale, D.; Kynoch, P.; Lehmann, H.;
Strelton, A. O. W.: Haemoglobin alpha(2) prime: alpha 2 gamma 2 (16
glycine to arginine). Nature 209: 1217-1218, 1966.

7. Barnabas, J.; Muller, C. J.: Haemoglobin Lepore (Hollandia). Nature 194:
931-932, 1962.

8. Beaven, G. H.; Gratzer, W. B.; Stevens, B. L.; Shooter, E. M.;
Ellis, M. J.; White, J. C.; Gillespie, J. E. O.: An abnormal haemoglobin
(Lepore-Cyprus) resembling haemoglobin Lepore and its interaction
with thalassaemia. Brit. J. Haemat. 10: 159-170, 1964.

9. Bennani, M.; Mombo, L.-E.; Chaventre, A.; Barakat, A.; Ducrocq,
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19. Edison, E. S.; Shaji, R. V.; Srivastava, A.; Chandy, M.: Compound
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21. Efremov, G. D.; Rudivic, R.; Niazi, G. A.; Hunter, E., Jr.; Huisman,
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22. Fessas, P.; Stamatoyannopoulos, G.; Karaklis, A.: Hemoglobin
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23. Fioretti, G.; De Angioletti, M.; Masciangelo, F.; Lacerra, G.;
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24. Frischknecht, H.; Dutly, F.: Two new delta-globin mutations:
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25. Fujita, S.; Ohta, Y.; Saito, S.; Kobayashi, Y.; Naritomi, Y.;
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26. Galanello, R.; Gasperini, D.; Perseu, L.; Barella, S.; Ideo, A.;
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27. Gasperini, D.; Perseu, L.; Cossu, P.; Podda, R.; Cao, A.; Galanello,
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29. Harano, T.; Harano, K.; Kushida, Y.; Ueda, S.; Kawakami, H.:
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30. Horton, B.; Payne, R. A.; Bridges, M. T.; Huisman, T. H. J.:
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31. Huehns, E. R.: A third haemoglobin abnormality in two individuals
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32. Huehns, E. R.; Dance, N.; Beaven, G. H.; Stevens, B. L.: Further
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33. Huisman, T. H. J.; Carver, M. F. H.: The beta- and delta-thalassemia
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34. Huisman, T. H. J.; Sydenstricker, V. P.: Haemoglobin: difference
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35. Jeffreys, A. J.: DNA sequence variants in the G-gamma, A-gamma,
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36. Jenkins, T.; Dunn, D. S.: Haematological genetics in the tropics.
Part I: Tropical Africa. Clin. Haemat. 10: 1029-1050, 1981.

37. Jones, R. T.; Brimhall, B.; Huehns, E. R.; Barnicot, N. A.: Hemoglobin
Sphakia: a delta-chain variant of hemoglobin A2 from Crete. Science 151:
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38. Jones, R. T.; Brimhall, B.; Huisman, T. H. J.: Structural characterization
of two delta chain variants: hemoglobin A-prime-2 (B2) and hemoglobin
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39. Juricic, D.; Crepinko, I.; Efremov, G. D.; Lam, H.; Webber, B.
B.; Headlee, M. G.; Huisman, T. H. J.: Hb A(2)-Zagreb or delta125(H3)gln-to-glu,
a new delta chain variant in association with delta-beta-thalassemia. Hemoglobin 7:
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40. Klein, H. L.; Petes, T. D.: Intrachromosomal gene conversion
in yeast. Nature 289: 144-148, 1981.

41. Labie, D.; Schroeder, W. A.; Huisman, T. H. J.: The amino acid
sequence of the delta-beta chains of haemoglobin Lepore Augusta =
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42. Lanclos, K. D.; Patterson, J.; Efremov, G. D.; Wong, S. C.; Villegas,
A.; Ojwang, P. J.; Wilson, J. B.; Kutlar, F.; Huisman, T. H. J.:
Characterization of chromosomes with hybrid genes for Hb Lepore-Washington,
Hb Lepore-Baltimore, Hb P-Nilotic, and Hb Kenya. Hum. Genet. 77:
40-45, 1987.

43. Lee, R. C.; Huisman, T. H. J.: A variant of hemoglobin A-2 found
in a Negro family. Blood 24: 495-501, 1964.

44. Lehmann, H.; Jenkins, T.; Plowman, D.; Nurse, G. T.: Homozygosity
for the delta-chain variant haemoglobin A(2)-prime (HbB-2) (delta16
gly-to-arg). Hemoglobin 9: 363-372, 1985.

45. Leung, H.; Gilbert, A. T.; Fleming, P. J.; Wong, J.; Hughes, W.
G.; Hussein, S.; Nash, A. R.: Hb A(2)-Parkville or delta47(CD6) asp-to-val,
a new delta chain variant. Hemoglobin 15: 407-416, 1991.

46. Lie-Injo, L. E.; Pribadi, W.; Westendorp-Boerma, F.; Efremov,
G. D.; Wilson, J. B.; Reynolds, C. A.; Huisman, T. H. J.: Hemoglobin
A(2)-Indonesia or alpha(2) beta(2) 69(E13)gly to arg. Biochim. Biophys.
Acta 229: 335-342, 1971.

47. Losekoot, M.; Fodde, R.; Giordano, P. C.; Bernini, L. F.: A novel
delta-0-thalassemia arising from a frameshift insertion, detected
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75-78, 1989.

48. Loudianos, G.; Cao, A.; Pirastu, M.; Vassilopoulos, G.; Kollia,
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1991.

49. Loudianos, G.; Murru, S.; Kanavakis, E.; Metaxotou-Mavromati,
A.; Theodoropoulou, D.; Kattamis, C.; Cao, A.; Pirastu, M.: A new
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50. Loudianos, G.; Murru, S.; Ristaldi, M. S.; Cossu, P.; Pilia, G.;
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51. Loudianos, G.; Porcu, S.; Cossu, P.; Tannoia, N.; Vitucci, A.;
Campanale, D.; Cao, A.; Pirastu, M.: A new delta-chain variant hemoglobin
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a family of southern Italian extraction. Hum. Mutat. 2: 327-329,
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52. Martin, S. L.; Zimmer, E. A.; Kan, Y. W.; Wilson, A. C.: Silent
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53. Matsuda, M.; Sakamoto, N.; Fukumaki, Y.: Delta-thalassemia caused
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1992.

54. Moi, P.; Loudianos, G.; Lavinha, J.; Murru, S.; Cossu, P.; Casu,
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55. Moi, P.; Paglietti, E.; Sanna, A.; Brancati, C.; Tagarelli, A.;
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1988.

56. Molchanova, T. P.; Postnikov, Y. V.; Gu, L.-H.; Huisman, T. H.
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57. Neeb, H.; Beiboer, J. L.; Jonxis, J. H.; Kaars-Sijpesteijn, J.
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58. Oggiano, L.; Pirastu, M.; Moi, P.; Longinotti, M.; Perseu, L.;
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59. Ohba, Y.; Igarashi, M.; Tsukahara, M.; Nakashima, M.; Sanada,
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60. Ostertag, W.; Smith, E. W.: Hemoglobin-Lepore-Baltimore, a third
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61. Papadakis, M.; Drakoulakou, O.; Papapanagiotou, E.; Pessini, D.;
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62. Petes, T. D.: Evidence that structural variants within the human
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63. Ramirez, F.; Mears, J. G.; Nudel, U.; Bank, A.; Luzzatto, L.;
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64. Ranney, H. M.; Jacobs, A. S.: Simultaneous occurrence of haemoglobins
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66. Renda, M.; Piazza, T.; Ciaccio, C.; Maggio, A.: Delta(+)-27 homozygosis
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67. Rieder, R. F.; Clegg, J. B.; Weiss, H. J.; Christy, N. P.; Rabinowitz,
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68. Romero Garcia, C.; Navarro, J. L.; Lam, H.; Webber, B. B.; Headlee,
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121(GH4) glu-to-val, an unstable delta chain variant observed in a
Spanish family. Hemoglobin 7: 435-442, 1983.

69. Salkie, M. L.; Gordon, P. A.; Rigal, W. M.; Lam, H.; Wilson, J.
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70. Schiliro, G.; Russo-Mancuso, G.; Dibenedetto, S. P.; Samperi,
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71. Sharma, R. S.; Harding, D. L.; Wong, S. D.; Wilson, J. B.; Gravely,
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233-235, 1974.

72. Sharma, R. S.; Williams, L.; Wilson, J. B.; Huisman, T. H. J.
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73. Spritz, R. A.; DeRiel, J. K.; Forget, B. G.; Weissman, S. M.:
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74. Spurdle, A. B.; Krause, A.; Ramsay, M.; Jenkins, T.: The high
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75. Trifillis, P.; Ioannou, P.; Schwartz, E.; Surrey, S.: Identification
of four novel delta-globin gene mutations in Greek Cypriots using
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analysis. Blood 78: 3298-3305, 1991.

76. Vella, F.; Graham, B.: A variant of hemoglobin A(2) in Alberta
Indians. Clin. Biochem. 2: 455-460, 1969.

77. Williamson, D.; Brennan, S. O.; Strosberg, H.; Whitty, J.; Carell,
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78. Wilson, J. T.; Wilson, L. B.; Ohta, Y.: A case of homozygous
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*FIELD* CN
Victor A. McKusick - updated: 10/3/2005
Victor A. McKusick - updated: 8/11/2005
Victor A. McKusick - updated: 9/2/2003
Anne M. Stumpf - updated: 11/27/2002
Victor A. McKusick - updated: 11/21/2002
Victor A. McKusick - updated: 5/23/2002

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Victor A. McKusick: 6/4/1986

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