RBCC Red Blood Cell Collection

LYZ (LZM) [Confidence: high (present in two of the MS resources)]
Lysozyme C; 3.2.1.17 (1,4-beta-N-acetylmuramidase C; Flags: Precursor)
Note: presumably soluble (membrane word is not in UniProt keywords or features)

hRBCD IPI00019038
IPI00019038 Lysozyme C precursor Lysozyme C precursor membrane n/a n/a n/a n/a n/a n/a n/a n/a 2 n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a extracellular n/a found at its expected molecular weight found at molecular weight

UniProt P61626
ID LYSC_HUMAN Reviewed; 148 AA.
AC P61626; P00695; Q13170; Q9UCF8;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
read moreDT 07-JUN-2004, sequence version 1.
DT 22-JAN-2014, entry version 117.
DE RecName: Full=Lysozyme C;
DE EC=3.2.1.17;
DE AltName: Full=1,4-beta-N-acetylmuramidase C;
DE Flags: Precursor;
GN Name=LYZ; Synonyms=LZM;
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].
RX PubMed=2971592; DOI=10.1016/0378-1119(88)90359-9;
RA Castanon M.J., Spevak W., Adolf G.R., Chlebowicz-Sledziewska E.,
RA Sledziewski A.;
RT "Cloning of human lysozyme gene and expression in the yeast
RT Saccharomyces cerevisiae.";
RL Gene 66:223-234(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3413092; DOI=10.1073/pnas.85.17.6227;
RA Chung L.P., Keshav S., Gordon S.;
RT "Cloning the human lysozyme cDNA: inverted Alu repeat in the mRNA and
RT in situ hybridization for macrophages and Paneth cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 85:6227-6231(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2829884; DOI=10.1016/0006-291X(88)90461-5;
RA Yoshimura K., Toibana A., Nakahama K.;
RT "Human lysozyme: sequencing of a cDNA, and expression and secretion by
RT Saccharomyces cerevisiae.";
RL Biochem. Biophys. Res. Commun. 150:794-801(1988).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2546758; DOI=10.1111/j.1432-1033.1989.tb14857.x;
RA Peters C.W.B., Kruse U., Pollwein R., Grzeschik K.H., Sippel A.E.;
RT "The human lysozyme gene. Sequence organization and chromosomal
RT localization.";
RL Eur. J. Biochem. 182:507-516(1989).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Huang B., Zhao C., Lei X., Cai L.;
RT "The cloning, sequencing and analysis of Chinese human lysozyme gene
RT cDNA amplified with RT-PCR from human placental total RNA.";
RL Sheng Wu Hua Hsueh Tsa Chih 9:269-273(1993).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Colon;
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 [7]
RP PROTEIN SEQUENCE OF 19-148.
RC TISSUE=Urine;
RX PubMed=5284421;
RA Canfield R.E., Kammerman S., Sobel H.H., Morgan F.J.;
RT "Primary structure of lysozymes from man and goose.";
RL Nature New Biol. 232:16-17(1971).
RN [8]
RP PROTEIN SEQUENCE OF 19-148, AND SEQUENCE REVISION TO 118.
RC TISSUE=Urine;
RX PubMed=11946554; DOI=10.1016/0014-5793(72)80212-6;
RA Thomsen J., Lund E.H., Kristiansen K., Brunfeldt K., Malmquist J.;
RT "A Val-Val sequence found in a human monocytic leukemia lysozyme.";
RL FEBS Lett. 22:34-36(1972).
RN [9]
RP PROTEIN SEQUENCE OF 19-148.
RC TISSUE=Milk;
RX PubMed=5168859; DOI=10.1002/hlca.19710540830;
RA Jolles J., Jolles P.;
RT "Human milk lysozyme: unpublished data concerning the establishment of
RT the complete primary structure; comparison with lysozymes of various
RT origins.";
RL Helv. Chim. Acta 54:2668-2675(1971).
RN [10]
RP PROTEIN SEQUENCE OF 19-148, AND SEQUENCE REVISION TO 118.
RC TISSUE=Milk;
RX PubMed=11946553; DOI=10.1016/0014-5793(72)80211-4;
RA Jolles J., Jolles P.;
RT "Comparison between human and bird lysozymes: note concerning the
RT previously observed deletion.";
RL FEBS Lett. 22:31-33(1972).
RN [11]
RP FOLDING, AND MUTAGENESIS.
RX PubMed=8503881;
RA Kanaya E., Ishihara K., Tsunasawa S., Nokihara K., Kikuchi M.;
RT "Indication of possible post-translational formation of disulphide
RT bonds in the beta-sheet domain of human lysozyme.";
RL Biochem. J. 292:469-476(1993).
RN [12]
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 [13]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
RA Banyard S.H., Blake C.C.F., Swan I.D.A.;
RT "The high resolution X-ray study of human. lysozyme: a preliminary
RT analysis.";
RL (In) Osserman E.F., Canfield R.E., Beychok S. (eds.);
RL Lysozyme, pp.71-79, Academic Press, New York (1974).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS).
RX PubMed=7334520; DOI=10.1016/0022-2836(81)90125-X;
RA Artymiuk P.J., Blake C.C.F.;
RT "Refinement of human lysozyme at 1.5-A resolution analysis of non-
RT bonded and hydrogen-bond interactions.";
RL J. Mol. Biol. 152:737-762(1981).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS).
RX PubMed=6876162; DOI=10.1016/S0022-2836(83)80105-3;
RA Blake C.C.F., Pulford W.C.A., Artymiuk P.J.;
RT "X-ray studies of water in crystals of lysozyme.";
RL J. Mol. Biol. 167:693-723(1983).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF MUTANT ALA-99 AND ALA-113.
RX PubMed=2061330;
RA Inaka K., Taniyama Y., Kikuchi M., Morikawa K., Matsushima M.;
RT "The crystal structure of a mutant human lysozyme C77/95A with
RT increased secretion efficiency in yeast.";
RL J. Biol. Chem. 266:12599-12603(1991).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (1.6 AND 1.1 ANGSTROMS).
RX PubMed=9757091; DOI=10.1107/S0907444997016922;
RA Steinrauf L.K.;
RT "Structures of monoclinic lysozyme iodide at 1.6 A and of triclinic
RT lysozyme nitrate at 1.1 A.";
RL Acta Crystallogr. D 54:767-780(1998).
RN [18]
RP STRUCTURE BY NMR.
RX PubMed=2207098; DOI=10.1021/bi00483a007;
RA Redfield C., Dobson C.M.;
RT "1H NMR studies of human lysozyme: spectral assignment and comparison
RT with hen lysozyme.";
RL Biochemistry 29:7201-7214(1990).
RN [19]
RP STRUCTURE BY NMR.
RX PubMed=1794972;
RA Ohkubo T., Taniyama Y., Kikuchi M.;
RT "1H and 15N NMR study of human lysozyme.";
RL J. Biochem. 110:1022-1029(1991).
RN [20]
RP VARIANTS AMYL8 THR-74 AND HIS-85.
RX PubMed=8464497; DOI=10.1038/362553a0;
RA Pepy M.B., Hawkins P.N., Booth D.R., Vigushin D.M., Tennent G.A.,
RA Soutar A.K., Totty N., Nguyen O., Blake C.C.F., Terry C.J.,
RA Feest T.G., Zalin A.M., Hsuan J.J.;
RT "Human lysozyme gene mutations cause hereditary systemic
RT amyloidosis.";
RL Nature 362:553-557(1993).
CC -!- FUNCTION: Lysozymes have primarily a bacteriolytic function; those
CC in tissues and body fluids are associated with the monocyte-
CC macrophage system and enhance the activity of immunoagents.
CC -!- CATALYTIC ACTIVITY: Hydrolysis of (1->4)-beta-linkages between N-
CC acetylmuramic acid and N-acetyl-D-glucosamine residues in a
CC peptidoglycan and between N-acetyl-D-glucosamine residues in
CC chitodextrins.
CC -!- SUBUNIT: Monomer.
CC -!- INTERACTION:
CC Self; NbExp=3; IntAct=EBI-355360, EBI-355360;
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- DISEASE: Amyloidosis 8 (AMYL8) [MIM:105200]: A hereditary
CC generalized amyloidosis due to deposition of apolipoprotein A1,
CC fibrinogen and lysozyme amyloids. Viscera are particularly
CC affected. There is no involvement of the nervous system. Clinical
CC features include renal amyloidosis resulting in nephrotic
CC syndrome, arterial hypertension, hepatosplenomegaly, cholestasis,
CC petechial skin rash. Note=The disease is caused by mutations
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: Lysozyme C is capable of both hydrolysis and
CC transglycosylation; it shows also a slight esterase activity. It
CC acts rapidly on both peptide-substituted and unsubstituted
CC peptidoglycan, and slowly on chitin oligosaccharides.
CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 22 family.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA32175.1; Type=Erroneous initiation;
CC -!- WEB RESOURCE: Name=GeneReviews;
CC URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/LYZ";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Lysozyme entry;
CC URL="http://en.wikipedia.org/wiki/Lysozyme";
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DR EMBL; M21119; AAA36188.1; -; mRNA.
DR EMBL; J03801; AAA59535.1; -; mRNA.
DR EMBL; M19045; AAA59536.1; -; mRNA.
DR EMBL; X14008; CAA32175.1; ALT_INIT; Genomic_DNA.
DR EMBL; U25677; AAC63078.1; -; mRNA.
DR EMBL; BC004147; AAH04147.1; -; mRNA.
DR PIR; S04938; LZHU.
DR RefSeq; NP_000230.1; NM_000239.2.
DR UniGene; Hs.524579; -.
DR PDB; 133L; X-ray; 1.77 A; A=19-148.
DR PDB; 134L; X-ray; 1.77 A; A=19-148.
DR PDB; 1B5U; X-ray; 1.80 A; A=19-148.
DR PDB; 1B5V; X-ray; 2.17 A; A=19-148.
DR PDB; 1B5W; X-ray; 2.17 A; A=19-148.
DR PDB; 1B5X; X-ray; 2.00 A; A=19-148.
DR PDB; 1B5Y; X-ray; 2.20 A; A=19-148.
DR PDB; 1B5Z; X-ray; 2.20 A; A/B=19-148.
DR PDB; 1B7L; X-ray; 1.80 A; A=19-148.
DR PDB; 1B7M; X-ray; 2.20 A; A=19-148.
DR PDB; 1B7N; X-ray; 1.80 A; A=19-148.
DR PDB; 1B7O; X-ray; 1.80 A; A=19-148.
DR PDB; 1B7P; X-ray; 2.00 A; A=19-148.
DR PDB; 1B7Q; X-ray; 2.00 A; A=19-148.
DR PDB; 1B7R; X-ray; 1.80 A; A=19-148.
DR PDB; 1B7S; X-ray; 2.00 A; A=19-148.
DR PDB; 1BB3; X-ray; 1.80 A; A/B=19-148.
DR PDB; 1BB4; X-ray; 2.23 A; A/B=19-148.
DR PDB; 1BB5; X-ray; 1.80 A; A/B=19-148.
DR PDB; 1C43; X-ray; 1.80 A; A=20-148.
DR PDB; 1C45; X-ray; 1.80 A; A=20-148.
DR PDB; 1C46; X-ray; 2.20 A; A=18-148.
DR PDB; 1C7P; X-ray; 2.40 A; A=19-148.
DR PDB; 1CJ6; X-ray; 1.80 A; A=19-148.
DR PDB; 1CJ7; X-ray; 1.80 A; A=19-148.
DR PDB; 1CJ8; X-ray; 1.80 A; A=19-148.
DR PDB; 1CJ9; X-ray; 1.80 A; A=19-148.
DR PDB; 1CKC; X-ray; 1.80 A; A=19-148.
DR PDB; 1CKD; X-ray; 1.80 A; A=19-148.
DR PDB; 1CKF; X-ray; 1.80 A; A=19-148.
DR PDB; 1CKG; X-ray; 2.20 A; A/B=19-148.
DR PDB; 1CKH; X-ray; 2.00 A; A=19-148.
DR PDB; 1D6P; X-ray; 2.23 A; A=19-148.
DR PDB; 1D6Q; X-ray; 1.96 A; A=19-148.
DR PDB; 1DI3; X-ray; 1.80 A; A=19-148.
DR PDB; 1DI4; X-ray; 2.00 A; A=19-148.
DR PDB; 1DI5; X-ray; 2.20 A; A=19-148.
DR PDB; 1EQ4; X-ray; 1.80 A; A=19-148.
DR PDB; 1EQ5; X-ray; 1.80 A; A=19-148.
DR PDB; 1EQE; X-ray; 1.80 A; A=19-148.
DR PDB; 1GAY; X-ray; 1.80 A; A=21-148.
DR PDB; 1GAZ; X-ray; 1.80 A; A=21-148.
DR PDB; 1GB0; X-ray; 1.80 A; A=21-148.
DR PDB; 1GB2; X-ray; 1.80 A; A=21-148.
DR PDB; 1GB3; X-ray; 1.80 A; A=21-148.
DR PDB; 1GB5; X-ray; 1.80 A; A=19-148.
DR PDB; 1GB6; X-ray; 1.80 A; A=19-148.
DR PDB; 1GB7; X-ray; 1.80 A; A=19-148.
DR PDB; 1GB8; X-ray; 1.80 A; A=19-148.
DR PDB; 1GB9; X-ray; 1.80 A; A=19-148.
DR PDB; 1GBO; X-ray; 1.80 A; A=19-148.
DR PDB; 1GBW; X-ray; 1.80 A; A=19-148.
DR PDB; 1GBX; X-ray; 1.80 A; A=19-148.
DR PDB; 1GBY; X-ray; 1.80 A; A=19-148.
DR PDB; 1GBZ; X-ray; 1.80 A; A=19-148.
DR PDB; 1GDW; X-ray; 1.80 A; A=19-148.
DR PDB; 1GDX; X-ray; 1.80 A; A=19-148.
DR PDB; 1GE0; X-ray; 1.80 A; A=19-148.
DR PDB; 1GE1; X-ray; 1.70 A; A=19-148.
DR PDB; 1GE2; X-ray; 2.00 A; A=19-148.
DR PDB; 1GE3; X-ray; 1.80 A; A=19-148.
DR PDB; 1GE4; X-ray; 1.80 A; A=19-148.
DR PDB; 1GEV; X-ray; 2.10 A; A=19-148.
DR PDB; 1GEZ; X-ray; 1.80 A; A=19-148.
DR PDB; 1GF0; X-ray; 1.80 A; A=19-148.
DR PDB; 1GF3; X-ray; 1.80 A; A=19-148.
DR PDB; 1GF4; X-ray; 1.80 A; A=19-148.
DR PDB; 1GF5; X-ray; 1.80 A; A=19-148.
DR PDB; 1GF6; X-ray; 1.80 A; A=19-148.
DR PDB; 1GF7; X-ray; 1.80 A; A=19-148.
DR PDB; 1GF8; X-ray; 1.80 A; A=21-148.
DR PDB; 1GF9; X-ray; 1.80 A; A=21-148.
DR PDB; 1GFA; X-ray; 1.80 A; A=21-148.
DR PDB; 1GFE; X-ray; 1.80 A; A=21-148.
DR PDB; 1GFG; X-ray; 1.80 A; A=21-148.
DR PDB; 1GFH; X-ray; 1.80 A; A=19-148.
DR PDB; 1GFJ; X-ray; 1.80 A; A=19-148.
DR PDB; 1GFK; X-ray; 1.80 A; A=19-148.
DR PDB; 1GFR; X-ray; 1.80 A; A=19-148.
DR PDB; 1GFT; X-ray; 1.80 A; A=19-148.
DR PDB; 1GFU; X-ray; 1.80 A; A=19-148.
DR PDB; 1GFV; X-ray; 1.80 A; A=19-148.
DR PDB; 1HNL; X-ray; 1.80 A; A=19-148.
DR PDB; 1I1Z; X-ray; 1.80 A; A=19-148.
DR PDB; 1I20; X-ray; 1.90 A; A=19-148.
DR PDB; 1I22; X-ray; 1.80 A; A/B/C/D=19-148.
DR PDB; 1INU; X-ray; 1.80 A; A=19-148.
DR PDB; 1IOC; X-ray; 2.40 A; A=19-148.
DR PDB; 1IP1; X-ray; 1.80 A; A=19-148.
DR PDB; 1IP2; X-ray; 1.80 A; A=19-148.
DR PDB; 1IP3; X-ray; 1.80 A; A/B=19-148.
DR PDB; 1IP4; X-ray; 1.80 A; A=19-148.
DR PDB; 1IP5; X-ray; 1.80 A; A=19-148.
DR PDB; 1IP6; X-ray; 1.80 A; A=19-148.
DR PDB; 1IP7; X-ray; 1.90 A; A/B=19-146.
DR PDB; 1IWT; X-ray; 1.40 A; A=19-148.
DR PDB; 1IWU; X-ray; 1.40 A; A=19-148.
DR PDB; 1IWV; X-ray; 1.40 A; A=19-148.
DR PDB; 1IWW; X-ray; 1.40 A; A=19-148.
DR PDB; 1IWX; X-ray; 1.40 A; A=19-148.
DR PDB; 1IWY; X-ray; 1.40 A; A=19-148.
DR PDB; 1IWZ; X-ray; 1.48 A; A=19-148.
DR PDB; 1IX0; X-ray; 1.80 A; A=19-148.
DR PDB; 1IY3; NMR; -; A=19-148.
DR PDB; 1IY4; NMR; -; A=19-148.
DR PDB; 1JKA; X-ray; 1.66 A; A=19-148.
DR PDB; 1JKB; X-ray; 1.66 A; A=19-148.
DR PDB; 1JKC; X-ray; 1.60 A; A=19-148.
DR PDB; 1JKD; X-ray; 1.80 A; A=19-148.
DR PDB; 1JSF; X-ray; 1.15 A; A=19-148.
DR PDB; 1JWR; X-ray; 1.40 A; A=19-148.
DR PDB; 1LAA; X-ray; 1.77 A; A=19-148.
DR PDB; 1LHH; X-ray; 1.80 A; A=19-148.
DR PDB; 1LHI; X-ray; 1.80 A; A=19-148.
DR PDB; 1LHJ; X-ray; 1.80 A; A=19-148.
DR PDB; 1LHK; X-ray; 1.80 A; A=19-148.
DR PDB; 1LHL; X-ray; 1.80 A; A=19-148.
DR PDB; 1LHM; X-ray; 1.80 A; A=19-148.
DR PDB; 1LMT; X-ray; 1.60 A; A=19-148.
DR PDB; 1LOZ; X-ray; 1.80 A; A=19-148.
DR PDB; 1LYY; X-ray; 1.80 A; A=19-148.
DR PDB; 1LZ1; X-ray; 1.50 A; A=19-148.
DR PDB; 1LZ4; X-ray; 1.80 A; A=19-148.
DR PDB; 1LZ5; X-ray; 1.80 A; A=19-144.
DR PDB; 1LZ6; X-ray; 1.80 A; A=19-148.
DR PDB; 1LZR; X-ray; 1.50 A; A=19-148.
DR PDB; 1LZS; X-ray; 1.60 A; A/B=19-148.
DR PDB; 1OP9; X-ray; 1.86 A; B=19-148.
DR PDB; 1OUA; X-ray; 1.80 A; A=19-148.
DR PDB; 1OUB; X-ray; 1.80 A; A=19-148.
DR PDB; 1OUC; X-ray; 1.80 A; A=19-148.
DR PDB; 1OUD; X-ray; 1.80 A; A=19-148.
DR PDB; 1OUE; X-ray; 1.80 A; A=19-148.
DR PDB; 1OUF; X-ray; 1.80 A; A=19-147.
DR PDB; 1OUG; X-ray; 1.80 A; A=21-148.
DR PDB; 1OUH; X-ray; 1.80 A; A=19-148.
DR PDB; 1OUI; X-ray; 1.80 A; A=19-148.
DR PDB; 1OUJ; X-ray; 1.80 A; A=19-148.
DR PDB; 1QSW; X-ray; 1.85 A; A/B/C/D=19-148.
DR PDB; 1RE2; X-ray; 2.30 A; A=19-148.
DR PDB; 1REM; X-ray; 2.10 A; A=19-148.
DR PDB; 1REX; X-ray; 1.50 A; A=19-148.
DR PDB; 1REY; X-ray; 1.70 A; A=19-148.
DR PDB; 1REZ; X-ray; 1.70 A; A=19-148.
DR PDB; 1TAY; X-ray; 1.70 A; A=19-148.
DR PDB; 1TBY; X-ray; 1.77 A; A=19-148.
DR PDB; 1TCY; X-ray; 1.70 A; A=19-148.
DR PDB; 1TDY; X-ray; 1.70 A; A=19-148.
DR PDB; 1UBZ; X-ray; 2.00 A; A=19-148.
DR PDB; 1W08; X-ray; 2.50 A; A=19-148.
DR PDB; 1WQM; X-ray; 1.80 A; A=19-148.
DR PDB; 1WQN; X-ray; 1.80 A; A=19-148.
DR PDB; 1WQO; X-ray; 1.80 A; A=19-148.
DR PDB; 1WQP; X-ray; 1.80 A; A=19-148.
DR PDB; 1WQQ; X-ray; 1.80 A; A=19-148.
DR PDB; 1WQR; X-ray; 1.80 A; A=19-148.
DR PDB; 1YAM; X-ray; 1.80 A; A=19-148.
DR PDB; 1YAN; X-ray; 1.80 A; A=19-148.
DR PDB; 1YAO; X-ray; 1.80 A; A=19-148.
DR PDB; 1YAP; X-ray; 1.80 A; A=19-148.
DR PDB; 1YAQ; X-ray; 1.80 A; A=19-148.
DR PDB; 207L; X-ray; 1.80 A; A=19-148.
DR PDB; 208L; X-ray; 2.20 A; A=19-148.
DR PDB; 2BQA; X-ray; 1.80 A; A=19-148.
DR PDB; 2BQB; X-ray; 1.80 A; A=19-148.
DR PDB; 2BQC; X-ray; 1.80 A; A=19-148.
DR PDB; 2BQD; X-ray; 1.80 A; A=19-148.
DR PDB; 2BQE; X-ray; 1.80 A; A=19-148.
DR PDB; 2BQF; X-ray; 1.80 A; A=19-148.
DR PDB; 2BQG; X-ray; 1.80 A; A=19-148.
DR PDB; 2BQH; X-ray; 1.80 A; A=19-148.
DR PDB; 2BQI; X-ray; 1.80 A; A=19-148.
DR PDB; 2BQJ; X-ray; 1.80 A; A=19-148.
DR PDB; 2BQK; X-ray; 1.80 A; A=19-147.
DR PDB; 2BQL; X-ray; 1.80 A; A=21-148.
DR PDB; 2BQM; X-ray; 1.80 A; A=19-148.
DR PDB; 2BQN; X-ray; 1.80 A; A=19-148.
DR PDB; 2BQO; X-ray; 1.80 A; A=19-148.
DR PDB; 2HEA; X-ray; 1.80 A; A=19-148.
DR PDB; 2HEB; X-ray; 2.20 A; A=19-148.
DR PDB; 2HEC; X-ray; 1.80 A; A=19-148.
DR PDB; 2HED; X-ray; 1.80 A; A=19-148.
DR PDB; 2HEE; X-ray; 1.80 A; A=19-148.
DR PDB; 2HEF; X-ray; 1.80 A; A=19-148.
DR PDB; 2LHM; X-ray; 1.80 A; A=19-148.
DR PDB; 2MEA; X-ray; 2.20 A; A/B=19-148.
DR PDB; 2MEB; X-ray; 1.80 A; A=19-148.
DR PDB; 2MEC; X-ray; 2.20 A; A/B=19-148.
DR PDB; 2MED; X-ray; 1.80 A; A=19-148.
DR PDB; 2MEE; X-ray; 1.80 A; A=19-148.
DR PDB; 2MEF; X-ray; 1.80 A; A=19-148.
DR PDB; 2MEG; X-ray; 1.80 A; A=19-148.
DR PDB; 2MEH; X-ray; 1.80 A; A=19-148.
DR PDB; 2MEI; X-ray; 1.80 A; A=19-148.
DR PDB; 2NWD; X-ray; 1.04 A; X=19-148.
DR PDB; 2ZIJ; X-ray; 1.90 A; A=19-148.
DR PDB; 2ZIK; X-ray; 1.81 A; A=19-148.
DR PDB; 2ZIL; X-ray; 1.80 A; A=19-148.
DR PDB; 2ZWB; Neutron; 1.80 A; A=19-148.
DR PDB; 3EBA; X-ray; 1.85 A; B=19-148.
DR PDB; 3FE0; X-ray; 1.50 A; A=19-148.
DR PDB; 3LHM; X-ray; 1.80 A; A=19-148.
DR PDB; 3LN2; X-ray; 2.04 A; A/B=19-148.
DR PDB; 4I0C; X-ray; 1.95 A; A/B=19-148.
DR PDBsum; 133L; -.
DR PDBsum; 134L; -.
DR PDBsum; 1B5U; -.
DR PDBsum; 1B5V; -.
DR PDBsum; 1B5W; -.
DR PDBsum; 1B5X; -.
DR PDBsum; 1B5Y; -.
DR PDBsum; 1B5Z; -.
DR PDBsum; 1B7L; -.
DR PDBsum; 1B7M; -.
DR PDBsum; 1B7N; -.
DR PDBsum; 1B7O; -.
DR PDBsum; 1B7P; -.
DR PDBsum; 1B7Q; -.
DR PDBsum; 1B7R; -.
DR PDBsum; 1B7S; -.
DR PDBsum; 1BB3; -.
DR PDBsum; 1BB4; -.
DR PDBsum; 1BB5; -.
DR PDBsum; 1C43; -.
DR PDBsum; 1C45; -.
DR PDBsum; 1C46; -.
DR PDBsum; 1C7P; -.
DR PDBsum; 1CJ6; -.
DR PDBsum; 1CJ7; -.
DR PDBsum; 1CJ8; -.
DR PDBsum; 1CJ9; -.
DR PDBsum; 1CKC; -.
DR PDBsum; 1CKD; -.
DR PDBsum; 1CKF; -.
DR PDBsum; 1CKG; -.
DR PDBsum; 1CKH; -.
DR PDBsum; 1D6P; -.
DR PDBsum; 1D6Q; -.
DR PDBsum; 1DI3; -.
DR PDBsum; 1DI4; -.
DR PDBsum; 1DI5; -.
DR PDBsum; 1EQ4; -.
DR PDBsum; 1EQ5; -.
DR PDBsum; 1EQE; -.
DR PDBsum; 1GAY; -.
DR PDBsum; 1GAZ; -.
DR PDBsum; 1GB0; -.
DR PDBsum; 1GB2; -.
DR PDBsum; 1GB3; -.
DR PDBsum; 1GB5; -.
DR PDBsum; 1GB6; -.
DR PDBsum; 1GB7; -.
DR PDBsum; 1GB8; -.
DR PDBsum; 1GB9; -.
DR PDBsum; 1GBO; -.
DR PDBsum; 1GBW; -.
DR PDBsum; 1GBX; -.
DR PDBsum; 1GBY; -.
DR PDBsum; 1GBZ; -.
DR PDBsum; 1GDW; -.
DR PDBsum; 1GDX; -.
DR PDBsum; 1GE0; -.
DR PDBsum; 1GE1; -.
DR PDBsum; 1GE2; -.
DR PDBsum; 1GE3; -.
DR PDBsum; 1GE4; -.
DR PDBsum; 1GEV; -.
DR PDBsum; 1GEZ; -.
DR PDBsum; 1GF0; -.
DR PDBsum; 1GF3; -.
DR PDBsum; 1GF4; -.
DR PDBsum; 1GF5; -.
DR PDBsum; 1GF6; -.
DR PDBsum; 1GF7; -.
DR PDBsum; 1GF8; -.
DR PDBsum; 1GF9; -.
DR PDBsum; 1GFA; -.
DR PDBsum; 1GFE; -.
DR PDBsum; 1GFG; -.
DR PDBsum; 1GFH; -.
DR PDBsum; 1GFJ; -.
DR PDBsum; 1GFK; -.
DR PDBsum; 1GFR; -.
DR PDBsum; 1GFT; -.
DR PDBsum; 1GFU; -.
DR PDBsum; 1GFV; -.
DR PDBsum; 1HNL; -.
DR PDBsum; 1I1Z; -.
DR PDBsum; 1I20; -.
DR PDBsum; 1I22; -.
DR PDBsum; 1INU; -.
DR PDBsum; 1IOC; -.
DR PDBsum; 1IP1; -.
DR PDBsum; 1IP2; -.
DR PDBsum; 1IP3; -.
DR PDBsum; 1IP4; -.
DR PDBsum; 1IP5; -.
DR PDBsum; 1IP6; -.
DR PDBsum; 1IP7; -.
DR PDBsum; 1IWT; -.
DR PDBsum; 1IWU; -.
DR PDBsum; 1IWV; -.
DR PDBsum; 1IWW; -.
DR PDBsum; 1IWX; -.
DR PDBsum; 1IWY; -.
DR PDBsum; 1IWZ; -.
DR PDBsum; 1IX0; -.
DR PDBsum; 1IY3; -.
DR PDBsum; 1IY4; -.
DR PDBsum; 1JKA; -.
DR PDBsum; 1JKB; -.
DR PDBsum; 1JKC; -.
DR PDBsum; 1JKD; -.
DR PDBsum; 1JSF; -.
DR PDBsum; 1JWR; -.
DR PDBsum; 1LAA; -.
DR PDBsum; 1LHH; -.
DR PDBsum; 1LHI; -.
DR PDBsum; 1LHJ; -.
DR PDBsum; 1LHK; -.
DR PDBsum; 1LHL; -.
DR PDBsum; 1LHM; -.
DR PDBsum; 1LMT; -.
DR PDBsum; 1LOZ; -.
DR PDBsum; 1LYY; -.
DR PDBsum; 1LZ1; -.
DR PDBsum; 1LZ4; -.
DR PDBsum; 1LZ5; -.
DR PDBsum; 1LZ6; -.
DR PDBsum; 1LZR; -.
DR PDBsum; 1LZS; -.
DR PDBsum; 1OP9; -.
DR PDBsum; 1OUA; -.
DR PDBsum; 1OUB; -.
DR PDBsum; 1OUC; -.
DR PDBsum; 1OUD; -.
DR PDBsum; 1OUE; -.
DR PDBsum; 1OUF; -.
DR PDBsum; 1OUG; -.
DR PDBsum; 1OUH; -.
DR PDBsum; 1OUI; -.
DR PDBsum; 1OUJ; -.
DR PDBsum; 1QSW; -.
DR PDBsum; 1RE2; -.
DR PDBsum; 1REM; -.
DR PDBsum; 1REX; -.
DR PDBsum; 1REY; -.
DR PDBsum; 1REZ; -.
DR PDBsum; 1TAY; -.
DR PDBsum; 1TBY; -.
DR PDBsum; 1TCY; -.
DR PDBsum; 1TDY; -.
DR PDBsum; 1UBZ; -.
DR PDBsum; 1W08; -.
DR PDBsum; 1WQM; -.
DR PDBsum; 1WQN; -.
DR PDBsum; 1WQO; -.
DR PDBsum; 1WQP; -.
DR PDBsum; 1WQQ; -.
DR PDBsum; 1WQR; -.
DR PDBsum; 1YAM; -.
DR PDBsum; 1YAN; -.
DR PDBsum; 1YAO; -.
DR PDBsum; 1YAP; -.
DR PDBsum; 1YAQ; -.
DR PDBsum; 207L; -.
DR PDBsum; 208L; -.
DR PDBsum; 2BQA; -.
DR PDBsum; 2BQB; -.
DR PDBsum; 2BQC; -.
DR PDBsum; 2BQD; -.
DR PDBsum; 2BQE; -.
DR PDBsum; 2BQF; -.
DR PDBsum; 2BQG; -.
DR PDBsum; 2BQH; -.
DR PDBsum; 2BQI; -.
DR PDBsum; 2BQJ; -.
DR PDBsum; 2BQK; -.
DR PDBsum; 2BQL; -.
DR PDBsum; 2BQM; -.
DR PDBsum; 2BQN; -.
DR PDBsum; 2BQO; -.
DR PDBsum; 2HEA; -.
DR PDBsum; 2HEB; -.
DR PDBsum; 2HEC; -.
DR PDBsum; 2HED; -.
DR PDBsum; 2HEE; -.
DR PDBsum; 2HEF; -.
DR PDBsum; 2LHM; -.
DR PDBsum; 2MEA; -.
DR PDBsum; 2MEB; -.
DR PDBsum; 2MEC; -.
DR PDBsum; 2MED; -.
DR PDBsum; 2MEE; -.
DR PDBsum; 2MEF; -.
DR PDBsum; 2MEG; -.
DR PDBsum; 2MEH; -.
DR PDBsum; 2MEI; -.
DR PDBsum; 2NWD; -.
DR PDBsum; 2ZIJ; -.
DR PDBsum; 2ZIK; -.
DR PDBsum; 2ZIL; -.
DR PDBsum; 2ZWB; -.
DR PDBsum; 3EBA; -.
DR PDBsum; 3FE0; -.
DR PDBsum; 3LHM; -.
DR PDBsum; 3LN2; -.
DR PDBsum; 4I0C; -.
DR ProteinModelPortal; P61626; -.
DR SMR; P61626; 19-148.
DR IntAct; P61626; 7.
DR MINT; MINT-5002660; -.
DR STRING; 9606.ENSP00000261267; -.
DR CAZy; GH22; Glycoside Hydrolase Family 22.
DR PhosphoSite; P61626; -.
DR DMDM; 48428995; -.
DR UCD-2DPAGE; P61626; -.
DR PaxDb; P61626; -.
DR PeptideAtlas; P61626; -.
DR PRIDE; P61626; -.
DR DNASU; 4069; -.
DR Ensembl; ENST00000261267; ENSP00000261267; ENSG00000090382.
DR GeneID; 4069; -.
DR KEGG; hsa:4069; -.
DR UCSC; uc001suw.2; human.
DR CTD; 4069; -.
DR GeneCards; GC12P069681; -.
DR HGNC; HGNC:6740; LYZ.
DR HPA; CAB000055; -.
DR MIM; 105200; phenotype.
DR MIM; 153450; gene.
DR neXtProt; NX_P61626; -.
DR Orphanet; 93561; Familial renal amyloidosis due to lysozyme variant.
DR PharmGKB; PA30503; -.
DR eggNOG; NOG85133; -.
DR HOGENOM; HOG000037357; -.
DR HOVERGEN; HBG052297; -.
DR InParanoid; P61626; -.
DR KO; K13915; -.
DR OMA; LQDNIAD; -.
DR OrthoDB; EOG7BW0M5; -.
DR PhylomeDB; P61626; -.
DR Reactome; REACT_116125; Disease.
DR ChiTaRS; LYZ; human.
DR EvolutionaryTrace; P61626; -.
DR GeneWiki; Lysozyme; -.
DR GenomeRNAi; 4069; -.
DR NextBio; 15952; -.
DR PRO; PR:P61626; -.
DR ArrayExpress; P61626; -.
DR Bgee; P61626; -.
DR CleanEx; HS_LYZ; -.
DR Genevestigator; P61626; -.
DR GO; GO:0005615; C:extracellular space; TAS:UniProtKB.
DR GO; GO:0003796; F:lysozyme activity; TAS:UniProtKB.
DR GO; GO:0016998; P:cell wall macromolecule catabolic process; IEA:InterPro.
DR GO; GO:0019835; P:cytolysis; IEA:UniProtKB-KW.
DR GO; GO:0042742; P:defense response to bacterium; IEA:UniProtKB-KW.
DR GO; GO:0006954; P:inflammatory response; TAS:UniProtKB.
DR InterPro; IPR001916; Glyco_hydro_22.
DR InterPro; IPR019799; Glyco_hydro_22_CS.
DR InterPro; IPR000974; Glyco_hydro_22_lys.
DR InterPro; IPR023346; Lysozyme-like_dom.
DR Pfam; PF00062; Lys; 1.
DR PRINTS; PR00137; LYSOZYME.
DR PRINTS; PR00135; LYZLACT.
DR SMART; SM00263; LYZ1; 1.
DR SUPFAM; SSF53955; SSF53955; 1.
DR PROSITE; PS00128; LACTALBUMIN_LYSOZYME_1; 1.
DR PROSITE; PS51348; LACTALBUMIN_LYSOZYME_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Amyloid; Amyloidosis; Antimicrobial;
KW Bacteriolytic enzyme; Complete proteome; Direct protein sequencing;
KW Disease mutation; Disulfide bond; Glycosidase; Hydrolase;
KW Polymorphism; Reference proteome; Secreted; Signal.
FT SIGNAL 1 18
FT CHAIN 19 148 Lysozyme C.
FT /FTId=PRO_0000018467.
FT ACT_SITE 53 53
FT ACT_SITE 71 71
FT DISULFID 24 146
FT DISULFID 48 134
FT DISULFID 83 99
FT DISULFID 95 113
FT VARIANT 74 74 I -> T (in AMYL8).
FT /FTId=VAR_004280.
FT VARIANT 85 85 D -> H (in AMYL8).
FT /FTId=VAR_004281.
FT VARIANT 88 88 T -> N (in dbSNP:rs1800973).
FT /FTId=VAR_012050.
FT CONFLICT 10 10 V -> A (in Ref. 5; AAC63078).
FT CONFLICT 41 41 I -> M (in Ref. 1; AAA36188).
FT CONFLICT 111 111 V -> A (in Ref. 5; AAC63078).
FT CONFLICT 124 124 I -> V (in Ref. 5; AAC63078).
FT CONFLICT 128 128 V -> A (in Ref. 5; AAC63078).
FT CONFLICT 136 136 N -> D (in Ref. 5; AAC63078).
FT HELIX 23 32
FT HELIX 38 40
FT HELIX 43 54
FT STRAND 55 57
FT STRAND 61 64
FT TURN 65 68
FT STRAND 69 72
FT TURN 73 76
FT TURN 79 82
FT STRAND 83 85
FT STRAND 88 90
FT HELIX 99 103
FT STRAND 104 106
FT HELIX 108 118
FT TURN 119 122
FT HELIX 123 126
FT HELIX 128 133
FT TURN 134 136
FT HELIX 140 142
FT TURN 143 145
SQ SEQUENCE 148 AA; 16537 MW; 8ECFD276BEB2678A CRC64;
MKALIVLGLV LLSVTVQGKV FERCELARTL KRLGMDGYRG ISLANWMCLA KWESGYNTRA
TNYNAGDRST DYGIFQINSR YWCNDGKTPG AVNACHLSCS ALLQDNIADA VACAKRVVRD
PQGIRAWVAW RNRCQNRDVR QYVQGCGV
//

MIM 105200
*RECORD*
*FIELD* NO
105200
*FIELD* TI
#105200 AMYLOIDOSIS, FAMILIAL VISCERAL
;;AMYLOIDOSIS VIII;;
OSTERTAG TYPE AMYLOIDOSIS;;
read moreGERMAN TYPE AMYLOIDOSIS;;
AMYLOIDOSIS, FAMILIAL RENAL;;
AMYLOIDOSIS, SYSTEMIC NONNEUROPATHIC
*FIELD* TX
A number sign (#) is used with this entry because of the evidence that
systemic nonneuropathic amyloidosis is the result of mutation in the
apolipoprotein A1 gene (APOA1; 107680), the fibrinogen alpha-chain gene
(FGA; 134820), the lysozyme gene (LYZ; 153450), or the gene encoding
beta-2-microglobulin (B2M; 109700).

CLINICAL FEATURES

Ostertag (1932, 1950) reported on a family with visceral amyloidosis. A
woman, 3 of her children, and 1 of her grandchildren were affected with
chronic nephropathy, arterial hypertension, and hepatosplenomegaly.
Albuminuria, hematuria and pitting edema were early signs. The age of
onset was variable. Death occurred about 10 years after onset. The
visceral involvement by amyloid was found to be extensive.

Maxwell and Kimbell (1936) described 3 brothers who died of visceral,
especially renal, amyloidosis in their 40s. Chronic weakness, edema,
proteinuria, and hepatosplenomegaly were features. McKusick (1974)
followed up on the family reported by Maxwell and Kimbell (1936). The
father of the 3 affected brothers died at age 72 after an automobile
accident and their mother died suddenly at age 87 after being in
apparent good health. A son of one of the brothers had frequent bouts of
unexplained fever in childhood (as did his father and 2 uncles),
accompanied at times by nonspecific rash. At the age of 35, proteinuria
was discovered and renal amyloidosis was diagnosed by renal biopsy. For
2 years thereafter he displayed the nephrotic syndrome, followed in the
next 2 years by uremia from which he died at age 39. Autopsy revealed
amyloidosis, most striking in the kidneys but also involving the adrenal
glands and spleen. Although some features of the family of Maxwell and
Kimbell (1936) are similar to those of urticaria, deafness and
amyloidosis (191900), no deafness was present in their family. Weiss and
Page (1974) reported a family with 2 definite and 4 probable cases in 3
generations.

Mornaghi et al. (1981, 1982) reported rapidly progressive biopsy-proved
renal amyloidosis in 3 brothers, aged 49, 52 and 55, of Irish-American
origin. None had evidence of a plasma cell dyscrasia, a monoclonal serum
or urine protein, or any underlying chronic disease. Immunoperoxidase
staining of 1 pulmonary and 1 renal biopsy specimen was negative for
amyloid A (AA), amyloid L (AL) and prealbumin. The authors concluded
that the disorder in the 3 brothers closely resembled that described by
Ostertag (1932).

Studying the proband of a kindred with the familial amyloidosis of
Ostertag, Lanham et al. (1982) demonstrated permanganate-sensitive
congophilia of the amyloid but found no immunofluorescent staining for
amyloid A or prealbumin. They concluded that this amyloid may be
chemically distinct from previously characterized forms.

Libbey and Talbert (1987) described a case of nephropathic amyloidosis,
presumably of the Ostertag type. In their case, the amyloid showed no
staining for light chains or prealbumin. Involvement of the liver was
associated with cholestasis. In the kindred reported by Lanham et al.
(1982), 6 members in 2 generations showed the onset of renal disease
between ages 23 and 45 years. The deposition of amyloid is
characteristically interstitial rather than glomerular as seen in other
forms of amyloidosis. The proband had the sicca syndrome. The details of
their patient's family history were not given by Libbey and Talbert
(1987).

Zalin et al. (1991) described yet another family with the Ostertag type
of familial nephropathic nonneuropathic amyloidosis. Petechial skin rash
was a striking feature, and petechial hemorrhages were induced by
minimal abrasion. Extensive amyloid deposition in the lungs was
illustrated. Zalin et al. (1991) reported that the amyloid deposits
contained apolipoprotein A-I; however, it was later shown that the
disorder in this family was caused by a mutation in lysozyme (see
153450.0001).

Vella et al. (2002) reported 2 patients with glaucoma due to primary
nonneuropathic amyloidosis. Glaucoma complicating amyloidosis had been
documented previously in familial amyloidotic polyneuropathy, and in
association with primary localized orbital amyloidosis. One of their
patients developed orbital amyloidoma and secondary glaucoma. After a
sudden worsening of visual acuity, papilledema was found and
(nonarteritic) anterior ischemic optic neuropathy was diagnosed. Tumor
debulking and orbital decompression were performed. Tumor histology
showed massive deposits of amyloid containing lambda chains.
Postoperatively, glaucoma was controllable with topical therapy. The
other patient had a 2-year history of weakness, persistent abdominal
pain, paresthesias, and weight loss, and a 20-year history of open-angle
glaucoma. This patient was found to have primary systemic amyloidosis on
liver and rectal biopsies. Echocardiography showed restrictive
cardiomyopathy with a diffuse hyperrefractile 'granular sparkling
appearance.' Intraocular pressure was normal on topical therapy and
ocular fundus examination showed hard drusen-like deposits bilaterally.
The patient's course improved after 15 cycles of melphalan-prednisone
treatment over 24 months. The authors stated that the incidence of
primary amyloidosis-associated glaucoma might be underestimated because
glaucoma in Western Europe and North America is less commonly treated
surgically.

MOLECULAR GENETICS

In the family with hereditary nonneuropathic systemic amyloidosis
previously studied by Zalin et al. (1991) and in another unrelated
English family with the disease, Pepys et al. (1993) identified
heterozygosity for 2 missense mutations in the LYZ gene, respectively
(153450.0001 and 153450.0002).

In a Peruvian family in which a brother and sister and the son of the
brother died from renal amyloidosis, Benson et al. (1993) identified a
mutation in the fibrinogen A alpha polypeptide gene (FGA; 134820.0012).

In 2 large American kindreds of Irish descent with nephrotic syndrome
due to renal amyloidosis, Uemichi et al. (1993, 1994) identified a
missense mutation in the FGA gene (E526V; 134820.0013).

In an American kindred with hereditary renal amyloidosis, Uemichi et al.
(1996) identified a 1-bp deletion in the FGA gene (134820.0016), causing
a frameshift and termination sequence at codon 548.

In a French kindred with autosomal dominant hereditary renal
amyloidosis, Asl et al. (1997) identified a different 1-bp deletion in
the FGA gene, also resulting in termination at codon 548 (134820.0018).

Systemic amyloidosis is the diagnosis in 2.5% of all renal biopsies,
according to Davison (1985), and is the cause of death in more than 1 in
1,500 persons in the United Kingdom annually. Acquired monoclonal
immunoglobulin light-chain amyloidosis (AL; see 254500), formerly known
as primary amyloidosis, is the most common form of systemic amyloidosis
and can respond to chemotherapy directed at the underlying plasma cell
dyscrasia. Lachmann et al. (2002) studied 350 patients with systemic
amyloidosis in whom a diagnosis of the AL type of the disorder had been
suggested by clinical and laboratory data and by the apparent absence of
a family history. They identified amyloidogenic mutations in 34 (9.7%)
of the patients, all of whom had the diagnosis of hereditary amyloidosis
confirmed by additional investigations. In 18 (5.1%) of the 350
patients, the E526V mutation in the FGA gene was identified; 13 of the
patients had missense mutations in the transthyretin gene (176330); 2
patients had missense mutations in the APOA1 gene (107680); and 1
patient had the D67H mutation in the lysozyme gene (153450.0002). All 18
patients with the FGA E526V mutation were of northern European ancestry,
and although none was aware of any relevant family history, genealogic
studies revealed that 2 were cousins and that ancestors of 2 other
patients lived in adjacent villages. A fifth patient retrospectively
ascertained that her dizygotic twin had died of renal failure at the age
of 76 years. The median age of the 18 patients at the time of
presentation was 59 years; the youngest was in her thirties and the
oldest was 78 years old. All presented with isolated renal dysfunction
and proteinuria, and most had moderate hypertension; all had renal
amyloid deposits, and splenic amyloid was present in all but 1 of the
patients. Spontaneous splenic rupture occurred in 2 patients.

Granel et al. (2005) described a patient diagnosed with systemic
digestive and 'medullar' amyloidosis. (Grateau (2006) stated that the
term 'medullar' referred to the involvement of bone marrow.) Primary
(AL) amyloidosis was initially suspected, but results of
immunohistochemical staining were negative for immunoglobulin
kappa/lambda light chains. The results of a complementary search for
lysozyme amyloidosis were positive in colonic mucosa. A missense
mutation, a T-to-A transversion at the first nucleotide of codon 64
(W64R; 153450.0005), was found in the LYZ gene. Granel et al. (2005)
pointed out that an incorrect diagnosis could have been made if complete
analysis of the amyloid deposits had not been performed, and that
amyloidoses of different types, i.e., AA, AL, transthyretin, lysozyme,
or fibrinogen, can produce similar visceral involvement, but prognosis
and treatment are completely different.

In 4 affected members of a family with autosomal dominant visceral
amyloidosis, Valleix et al. (2012) identified a heterozygous mutation in
the B2M gene (D76N; 109700.0002). Studies on the recombinant D76N
protein showed reduced stability of the fully folded mutant protein and
significantly increased conversion of the mutant protein into fibrils
with amyloid-like properties under physiologic conditions, whereas the
wildtype protein did not aggregate at all. In mid-adult life, the
patients developed slowly progressive chronic diarrhea with weight loss
and sicca syndrome. One had sensorimotor axonal polyneuropathy and
orthostatic hypotension and 2 had severe autonomic neuropathy.
Postmortem examination of 1 patient, who died at age 70 years, showed
extensive B2M-containing amyloid deposits in the spleen, liver, heart,
salivary glands, and nerves. Colonic biopsy from another affected
individual also contained B2M-containing amyloid deposits. Amyloid
scinotography of 2 patients showed a heavy visceral amyloid burden in
the spleen and adrenal glands, but not in heart. Valleix et al. (2012)
noted that the amyloid deposition in this family was different from that
observed in dialysis-related amyloidosis, in which B2M-amyloid
accumulates around bones and joints. In addition, serum B2M was not
increased in the patients with familial disease, whereas it is increased
in those with dialysis-related amyloidosis.

CLINICAL MANAGEMENT

Bodin et al. (2010) demonstrated that administration of anti-human serum
amyloid P component (SAP; 104770) antibodies to mice with amyloid
deposits containing human SAP triggers a potent, complement-dependent,
macrophage-derived giant cell reaction that swiftly removes massive
visceral amyloid deposits without adverse effects. Anti-SAP antibody
treatment is clinically feasible because circulating human SAP can be
depleted in patients by the bis-D-proline compound CPHPC, thereby
enabling injected anti-SAP antibodies to reach residual SAP in the
amyloid deposits.

*FIELD* SA
Alexander and Atkins (1975); Weiss and Page (1973)
*FIELD* RF
1. Alexander, F.; Atkins, E. L.: Familial renal amyloidosis: case
reports, literature review and classification. Am. J. Med. 59: 121-128,
1975.

2. Asl, L. H.; Liepnieks, J. J.; Uemichi, T.; Rebibou, J.-M.; Justrabo,
E.; Droz, D.; Mousson, C.; Chalopin, J.-M.; Benson, M. D.; Delpech,
M.; Grateau, G.: Renal amyloidosis with a frame shift mutation in
fibrinogen A(alpha)-chain gene producing a novel amyloid protein. Blood 90:
4799-4805, 1997.

3. Benson, M. D.; Liepnieks, J.; Uemichi, T.; Wheeler, G.; Correa,
R.: Hereditary renal amyloidosis associated with a mutant fibrinogen
alpha-chain. Nature Genet. 3: 252-255, 1993.

4. Bodin, K.; Ellmerich, S.; Kahan, M. C.; Tennent, G. A.; Loesch,
A.; Gilbertson, J. A.; Hutchinson, W. L.; Mangione, P. P.; Gallimore,
J. R.; Millar, D. J.; Minogue, S.; Dhillon, A. P.; Taylor, G. W.;
Bradwell, A. R.; Petrie, A.; Gillmore, J. D.; Bellotti, V.; Botto,
M.; Hawkins, P. N.; Pepys, M. B.: Antibodies to human serum amyloid
P component eliminate visceral amyloid deposits. Nature 468: 93-97,
2010.

5. Davison, A. M.: The United Kingdom Medical Research Council's
glomerulonephritis registry. Contrib. Nephrol. 48: 24-35, 1985.

6. Granel, B.; Serratrice, J.; Disdier, P.; Weiller, P.-J.; Valleix,
S.; Grateau, G.; Droz, D.: Underdiagnosed amyloidosis: amyloidosis
of lysozyme variant. Am. J. Med. 118: 321-323, 2005.

7. Grateau, G.: Personal Communication. Paris, France 1/16/2006.

8. Lachmann, H. J.; Chir, B.; Booth, D. R.; Booth, S. E.; Bybee, A.;
Gilbertson, J. A.; Gillmore, J. D.; Pepys, M. B.; Hawkins, P. N.:
Misdiagnosis of hereditary amyloidosis as AL (primary) amyloidosis. New
Eng. J. Med. 346: 1786-1791, 2002.

9. Lanham, J. G.; Meltzer, M. L.; de Beer, F. C.; Hughes, G. R. V.;
Pepys, M. B.: Familial amyloidosis of Ostertag. Quart. J. Med. 51:
25-32, 1982.

10. Libbey, C. A.; Talbert, M. L.: A 43-year-old woman with hepatic
failure after renal transplantation because of amyloidosis. New Eng.
J. Med. 317: 1520-1531, 1987.

11. Maxwell, E. S.; Kimbell, I.: Familial amyloidosis with case reports. Med.
Bull. Vet. Admin. 12: 365-369, 1936.

12. McKusick, V. A.: Personal Communication. Baltimore, Md. 1974.

13. Mornaghi, R.; Rubinstein, P.; Franklin, E. C.: Studies of the
pathogenesis of a familial form of renal amyloidosis. Trans. Assoc.
Am. Phys. 94: 211-216, 1981.

14. Mornaghi, R.; Rubinstein, P.; Franklin, E. C.: Familial renal
amyloidosis: case reports and genetic studies. Am. J. Med. 73: 609-614,
1982.

15. Ostertag, B.: Demonstration einer eigenartigen familiaeren Paramyloidose. Zbl.
Path. 56: 253-254, 1932.

16. Ostertag, B.: Familiaere Amyloid-erkrankung. Z. Menschl. Vererb.
Konstitutionsl. 30: 105-115, 1950.

17. Pepys, M. B.; Hawkins, P. N.; Booth, D. R.; Vigushin, D. M.; Tennent,
G. A.; Soutar, A. K.; Totty, N.; Nguyen, O.; Blake, C. C. F.; Terry,
C. J.; Feest, T. G.; Zalin, A. M.; Hsuan, J. J.: Human lysozyme gene
mutations cause hereditary systemic amyloidosis. Nature 362: 553-557,
1993.

18. Uemichi, T.; Liepnieks, J. J.; Benson, M. D.: Fibrinogen Indianapolis:
a fibrinogen A-alpha chain associated with hereditary amyloidosis.
(Abstract) Clin. Res. 41: 133 only, 1993.

19. Uemichi, T.; Liepnieks, J. J.; Benson, M. D.: Hereditary renal
amyloidosis with a novel variant fibrinogen. J. Clin. Invest. 93:
731-736, 1994.

20. Uemichi, T.; Liepnieks, J. J.; Yamada, T.; Gertz, M. A.; Bang,
N.; Benson, M. D.: A frame shift mutation in the fibrinogen A-alpha
chain gene in a kindred with renal amyloidosis. Blood 87: 4197-4203,
1996.

21. Valleix, S.; Gillmore, J. D.; Bridoux, F.; Mangione, P. P.; Dogan,
A.; Nedelec, B.; Boimard, M.; Touchard, G.; Goujon, J.-M.; Lacombe,
C.; Lozeron, P.; Adams, D.; and 14 others: Hereditary systemic
amyloidosis due to asp76asn variant beta-2-microglobulin. New Eng.
J. Med. 366: 2276-2283, 2012.

22. Vella, F. S.; Simone, B.; Giannelli, G.; Sisto, D.; Sborgio, C.;
Antonaci, S.: Glaucoma in primary amyloidosis: a fortuitous or causative
association? (Letter) Am. J. Med. 113: 252-254, 2002.

23. Weiss, S. W.; Page, D. L.: Amyloid nephropathy of Ostertag with
special reference to renal glomerular giant cells. Am. J. Path. 72:
447-460, 1973.

24. Weiss, S. W.; Page, D. L.: Amyloid nephropathy of Ostertag: report
of a kindred. Birth Defects Orig. Art. Ser. X(4): 67-68, 1974.

25. Zalin, A. M.; Jones, S.; Fitch, N. J. S.; Ramsden, D. B.: Familial
nephropathic non-neuropathic amyloidosis: clinical features, immunohistochemistry
and chemistry. Quart. J. Med. 81: 945-956, 1991.

*FIELD* CS

GI:
Hepatomegaly;
Cholestasis;
Splenomegaly

GU:
Nephropathy with hematuria;
Nephrotic syndrome;
Uremia

Endocrine:
Hypertension

Skin:
Pitting edema;
Petechial skin rash

Neuro:
Nonneuropathic

Misc:
Chronic weakness

Lab:
Generalized amyloid deposition;
Proteinuria;
Hematuria

Inheritance:
Autosomal dominant

*FIELD* CN
Cassandra L. Kniffin - updated: 6/14/2012
Ada Hamosh - updated: 1/4/2011
Marla J. F. O'Neill - updated: 1/8/2009
Victor A. McKusick - updated: 2/1/2006
Jane Kelly - updated: 3/20/2003
Victor A. McKusick - updated: 1/12/2001

*FIELD* CD
Victor A. McKusick: 6/4/1986

*FIELD* ED
alopez: 06/14/2012
ckniffin: 6/14/2012
alopez: 1/4/2011
terry: 1/4/2011
carol: 1/8/2009
carol: 2/1/2006
terry: 2/1/2006
wwang: 3/23/2005
wwang: 3/16/2005
cwells: 3/20/2003
carol: 9/11/2002
cwells: 1/18/2001
terry: 1/12/2001
carol: 4/6/1994
mimadm: 3/11/1994
carol: 5/17/1993
carol: 5/12/1993
carol: 5/6/1993
carol: 3/22/1993

MIM 153450
*RECORD*
*FIELD* NO
153450
*FIELD* TI
*153450 LYSOZYME; LYZ
*FIELD* TX

DESCRIPTION

Lysozyme (EC 3.2.1.17) catalyzes the hydrolysis of certain
read moremucopolysaccharides of bacterial cell walls. Specifically, it catalyzes
the hydrolysis of the bacterial cell wall beta(1-4) glycosidic linkages
between N-acetylmuramic acid and N-acetylglucosamine. It is found in
spleen, lung, kidney, white blood cells, plasma, saliva, milk, and
tears.

CLONING

Yoshimura et al. (1988) isolated a cDNA encoding human lysozyme from a
human placenta cDNA library. The 1.5-kb cDNA coded for a signal peptide
consisting of 18 amino acids and for mature lysozyme. The amino acid
sequence of the mature lysozyme, deduced from the nucleotide sequence,
was identical to the published sequence. Human lysozyme has 130 amino
acid residues and 4 disulfide bonds (Taniyama et al., 1991).

Peters et al. (1989) described the isolation of 2 overlapping genomic
clones containing 25 kb of the human lysozyme gene region. They also
isolated a full-length human lysozyme cDNA clone from a human placental
cDNA library. They reported on the nucleotide sequence of the entire
structural gene and the cDNA clone.

GENE FUNCTION

Canet et al. (1999) studied the unfolding and refolding properties of
human lysozyme and 2 of its amyloidogenic variants, ile56 to thr and
asp67 to his, by stopped-flow fluorescence and hydrogen exchange pulse
labeling coupled with mass spectrometry. Their results suggested that
the amyloidogenic nature of the lysozyme variants arises from a decrease
in the stability of the native fold relative to partially folded
intermediates. The origin of this instability was different in the 2
variants, being caused in one case primarily by a reduction in the
folding rate and in the other by an increase in the unfolding rate. In
both cases, this resulted in a low population of soluble partially
folded species that can aggregate in a slow and controlled manner to
form amyloid fibrils.

Dumoulin et al. (2003) reported that a single-domain fragment of a
camelid antibody raised against wildtype human lysozyme inhibited the in
vitro aggregation of its amyloidogenic variant, D67H (153450.0002).
Structural studies revealed that the epitope includes neither the site
of mutation nor most residues in the region of the protein structure
that is destabilized by the mutation. Instead, the binding of the
antibody fragment achieves its affect by restoring the structural
cooperativity characteristic of the wildtype protein. Dumoulin et al.
(2003) suggested that this appears to occur at least in part through the
transmission of long-range conformational effects to the interface
between the 2 structural domains of the protein.

MAPPING

Using a panel of somatic cell hybrids, Peters et al. (1989) assigned the
lysozyme gene to human chromosome 12.

MOLECULAR GENETICS

In the human, mutations in the LYZ gene in familial visceral amyloidosis
(105200) represented the first definitive link of lysozyme to genetic
disease (see 153450.0001).

ANIMAL MODEL

Prieur et al. (1974) described inherited lysozyme deficiency in rabbits.
No abnormality of cartilage or bone was noted (Greenwald et al., 1975).
Older mutant rabbits showed increased susceptibility to infections,
especially subcutaneous abscesses (Prieur, 1975). Camara et al. (1990)
identified 2 isozymes of rabbit lysozyme and showed that their
distribution was tissue specific. Leukocytic and gastrointestinal
isozymes were clearly distinguished, and a possible lymphoepithelial
isozyme that resembled the gastrointestinal isozyme electrophoretically
and chromatographically but not kinetically was demonstrated. Mutant,
lysozyme-deficient rabbits completely lacked a detectable leukocytic
isozyme but had gastrointestinal and lymphoepithelial isozymes
indistinguishable from those of normal rabbits. By electrophoretic
methods, the mutant rabbits were shown to lack a protein band
corresponding to that of the leukocytic isozyme in normal rabbits.

HISTORY

Alexander Fleming (1881-1955), of penicillin fame, discovered and named
lysozyme. In a communication to the Royal Society, Fleming (1922) wrote:
'...I wish to draw attention to a substance present in the tissues and
secretions of the body, which is capable of rapidly dissolving certain
bacteria. As this substance has properties akin to those of ferments I
have called it a Lysozyme....' Fleming and Allison (1922) demonstrated
an unusually high concentration in cartilage, indeed the highest of any
tissue. It resembles lactalbumin (149750) in structure. Human lysozyme
has a molecular mass of 14,602 Da. Neufeld (1972) suggested that a
genetic defect of lysozyme might underlie a skeletal dysplasia.

*FIELD* AV
.0001
AMYLOIDOSIS, FAMILIAL VISCERAL
LYZ, ILE56THR

Pepys et al. (1993) described mutations of the LYZ gene in association
with hereditary nonneuropathic systemic amyloidosis (105200) in 2
unrelated English families. Affected persons were heterozygous for point
mutations that caused substitution of highly conserved residues, namely,
threonine for isoleucine at position 56 in 1 family, and histidine for
aspartic acid at residue 67 in the other (153450.0002). Amyloid fibrils
from 1 individual were composed of the full-length thr56 variant
lysozyme molecule. They commented on the fact that the amyloidosis was
of the Ostertag type (105200). In 1 of the families, Zalin et al. (1991)
had incorrectly reported that the amyloid deposits contained
apolipoprotein A-I (107680), a previously known cause of renal
amyloidosis. Petechial skin rash was a striking feature in that family,
and petechial hemorrhages were induced by minimal abrasion. Extensive
amyloid deposition in the lungs was illustrated.

.0002
AMYLOIDOSIS, FAMILIAL VISCERAL
LYZ, ASP67HIS

See 153450.0001 and Pepys et al. (1993).

The asp67-to-his (D67H) mutation in the LYZ gene was present in affected
members of the family reported by Harrison et al. (1996), in which
spontaneous hepatic hemorrhage with rupture of the liver occurred. The
proband, a 15-year-old boy, underwent emergency laporotomy for massive
intraabdominal hemorrhage related to a hepatic bleed and a large
capsular hematoma. At transplantation, the liver was noted to be
remarkably fragile and friable, with loss of the reticulin framework.
The proband's father had previously undergone laporotomy for massive
hepatic bleeds and died of uncontrollable intraabdominal bleeding. The
paternal grandfather had also died shortly after uncontrollable hepatic
hemorrhage.

The D67H mutation was present in affected members of the family reported
by Gillmore et al. (1999) in which severe renal disease dominated the
clinical picture.

.0003
AMYLOIDOSIS, FAMILIAL VISCERAL
LYZ, TRP64ARG, T-C

Valleix et al. (2002) studied a French family with a history of
autosomal dominant hereditary amyloidosis (105200) with early sicca
syndrome (see 270150) and nephropathy leading to renal failure after the
fifth to seventh decade. Valleix et al. (2002) identified a
tryptophan-to-arginine substitution at codon 64 (W64R), resulting from a
T-C nucleotide transition in the LYZ gene, in affected family members
but not in unaffected family members.

Also see 153450.0005.

.0004
AMYLOIDOSIS, FAMILIAL VISCERAL
LYZ, PHE57ILE

In an Italian Canadian family segregating autosomal dominant familial
visceral amyloidosis (105200), Yazaki et al. (2003) identified a T-to-A
transversion in the LYZ gene, resulting in a phe-to-ile substitution at
residue 57 (F57I). The proband developed renal failure at the age of 42,
but a younger sister and daughter also had renal amyloidosis.

.0005
AMYLOIDOSIS, FAMILIAL VISCERAL
LYZ, TRP64ARG, T-A

In a 59-year-old woman from Piedmont, Italy, with hereditary lysozyme
amyloidosis (105200), mainly characterized by gastrointestinal
involvement, Granel et al. (2002) identified heterozygosity for a T-to-A
transition in the LYZ gene, resulting in a W64R substitution.

In a 62-year-old woman from Piedmont, Italy, who was presumably
unrelated to the patient reported by Granel et al. (2002), Granel et al.
(2005) identified the same T-to-A mutation leading to the W64R
substitution. The patient was diagnosed as having systemic digestive and
'medullar' amyloidosis. Grateau (2006) stated that the term 'medullar'
referred to involvement of the bone marrow.

In a 33-year-old English man with lysozyme amyloidosis, Granel et al.
(2006) identified the same T-to-A mutation. This patient had a dramatic
bleeding episode due to rupture of abdominal lymph nodes.

Also see 153450.0003.

*FIELD* SA
Dayhoff (1972)
*FIELD* RF
1. Camara, V. M.; Harding, J. W.; Prieur, D. J.: Inherited lysozyme
deficiency in rabbits: the absence of a primary isozyme of lysozyme
as the cause of the condition. Lab. Invest. 63: 544-550, 1990.

2. Canet, D.; Sunde, M.; Last, A. M.; Miranker, A.; Spencer, A.; Robinson,
C. V.; Dobson, C. M.: Mechanistic studies of the folding of human
lysozyme and the origin of amyloidogenic behavior in its disease-related
variants. Biochemistry 38: 6419-6427, 1999.

3. Dayhoff, M. O.: Atlas of Protein Sequence and Structure. Lactalbumin
and Lysozyme. Washington: National Biomedical Research Foundation
(pub.) 5: 1972. Pp. D133-D140.

4. Dumoulin, M.; Last, A. M.; Desmyter, A.; Decanniere, K.; Canet,
D.; Larsson, G.; Spencer, A.; Archer, D. B.; Sasse, J.; Muyldermans,
S.; Wyns, L.; Redfield, C.; Matagne, A.; Robinson, C. V.; Dobson,
C. M.: A camelid antibody fragment inhibits the formation of amyloid
fibrils by human lysozyme. Nature 424: 783-788, 2003.

5. Fleming, A.: On a remarkable bacteriolytic element found in tissues
and secretions. Proc. Roy. Soc. Ser. B. 93: 306-317, 1922.

6. Fleming, A.; Allison, V. D.: Observations on a bacteriolytic substance
('lysozyme') found in secretions and tissues. Brit. J. Exp. Path. 3:
252-260, 1922.

7. Gillmore, J. D.; Booth, D. R.; Madhoo, S.; Pepys, M. B.; Hawkins,
P. N.: Hereditary renal amyloidosis associated with variant lysozyme
in a large English family. Nephrol. Dial. Transplant. 14: 2639-2644,
1999.

8. Granel, B.; Serratrice, J.; Disdier, P.; Weiller, P.-J.; Valleix,
S.; Grateau, G.; Droz, D.: Underdiagnosed amyloidosis: amyloidosis
of lysozyme variant. (Letter) Am. J. Med. 118: 321-323, 2005.

9. Granel, B.; Serratrice, J.; Valleix, S.; Grateau, G.; Droz, D.;
Lafon, J.; Sault, M.-C.; Chaudier, B.; Disdier, P.; Laugier, R.; Delpech,
M.; Weiller, P.-J.: A family with gastrointestinal amyloidosis associated
with variant lysozyme. Gastroenterology 123: 1346-1349, 2002.

10. Granel, B.; Valleix, S.; Serratrice, J.; Cherin, P.; Texeira,
A.; Disdier, P.; Weiller, P.-J.; Grateau, G.: Lysozyme amyloidosis:
report of 4 cases and a review of the literature. Medicine 85: 66-73,
2006.

11. Grateau, G.: Personal Communication. Paris, France 1/16/2006.

12. Greenwald, R. A.; Cantor, J. O.; Prieur, D. J.; Young, D. M.:
Composition of cartilage from lysozyme-deficient rabbits. Biochim.
Biophys. Acta 385: 435-437, 1975.

13. Harrison, R. F.; Hawkins, P. N.; Roche, W. R.; MacMahon, R. F.
T.; Hubscher, S. G.; Buckels, J. A. C.: 'Fragile' liver and massive
hepatic haemorrhage due to hereditary amyloidosis. Gut 38: 151-152,
1996.

14. Neufeld, E. L.: Personal Communication. Bethesda, Maryland
1972.

15. Pepys, M. B.; Hawkins, P. N.; Booth, D. R.; Vigushin, D. M.; Tennent,
G. A.; Soutar, A. K.; Totty, N.; Nguyen, O.; Blake, C. C. F.; Terry,
C. J.; Feest, T. G.; Zalin, A. M.; Hsuan, J. J.: Human lysozyme gene
mutations cause hereditary systemic amyloidosis. Nature 362: 553-557,
1993.

16. Peters, C. W. B.; Kruse, U.; Pollwein, R.; Grzeschik, K.-H.; Sippel,
A. E.: The human lysozyme gene: sequence organization and chromosomal
localization. (Abstract) Cytogenet. Cell Genet. 51: 1059 only, 1989.

17. Prieur, D. J.: Personal Communication. Pullman, Washington
5/13/1975.

18. Prieur, D. J.; Olson, H. M.; Young, D. M.: Lysozyme deficiency--an
inherited disorder of rabbits. Am. J. Path. 77: 283-296, 1974.

19. Taniyama, Y.; Kuroki, R.; Omura, F.; Seko, C.; Kikuchi, M.: Evidence
for intramolecular disulfide bond shuffling in the folding of mutant
human lysozyme. J. Biol. Chem. 266: 6456-6461, 1991.

20. Valleix, S.; Drunat, S.; Philit, J.-B.; Adoue, D.; Piette, J.-C.;
Droz, D.; MacGregor, B.; Canet, D.; Delpech, M.; Grateau, G.: Hereditary
renal amyloidosis caused by a new variant lysozyme W64R in a French
family. Kidney Int. 61: 907-912, 2002.

21. Yazaki, M.; Farrell, S. A.; Benson, M. D.: A novel lysozyme mutation
phe57ile associated with hereditary renal amyloidosis. Kidney Int. 63:
1652-1657, 2003.

22. Yoshimura, K.; Toibana, A.; Nakahama, K.: Human lysozyme: sequencing
of a cDNA, and expression and secretion by Saccharomyces cerevisiae. Biochem.
Biophys. Res. Commun. 150: 794-801, 1988.

23. Zalin, A. M.; Jones, S.; Fitch, N. J. S.; Ramsden, D. B.: Familial
nephropathic non-neuropathic amyloidosis: clinical features, immunohistochemistry
and chemistry. Quart. J. Med. 81: 945-956, 1991.

*FIELD* CN
Victor A. McKusick - updated: 1/31/2006
Victor A. McKusick - updated: 1/9/2006
Victor A. McKusick - updated: 4/21/2005
Victor A. McKusick - updated: 3/10/2005
Ada Hamosh - updated: 8/26/2003
Victor A. McKusick - updated: 1/19/2000
Victor A. McKusick - updated: 10/26/1999

*FIELD* CD
Victor A. McKusick: 6/2/1986

*FIELD* ED
terry: 09/08/2010
carol: 1/8/2009
carol: 1/31/2006
terry: 1/9/2006
tkritzer: 4/27/2005
terry: 4/21/2005
alopez: 3/24/2005
wwang: 3/16/2005
terry: 3/10/2005
terry: 3/9/2005
alopez: 8/26/2003
terry: 8/26/2003
mcapotos: 1/28/2000
mcapotos: 1/24/2000
terry: 1/19/2000
carol: 11/3/1999
terry: 10/26/1999
mark: 6/7/1996
davew: 7/13/1994
warfield: 4/21/1994
carol: 11/24/1993
carol: 5/21/1993
carol: 5/17/1993
carol: 5/6/1993