Von Willebrand Disease: A Database of Point Mutations, Insertions, and Deletions

David Ginsburg; Evan J Sadler

doi:10.1055/s-0038-1651576

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 1993; 69(02): 177-184
DOI: 10.1055/s-0038-1651576

Original Article

Von Willebrand Disease

Schattauer GmbH Stuttgart

Von Willebrand Disease: A Database of Point Mutations, Insertions, and Deletions

For the Consortium on von Willebrand Factor Mutations and Polymorphisms^[1], and the Subcommittee on von Willebrand Factor of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis

David Ginsburg

^*The Howard Hughes Medical Institute, Departments of Internal Medicine and Human Genetics, University of Michigan Medical School, Ann Arbor, MI, USA

,

Evan J Sadler

^**The Howard Hughes Medical Institute, The Jewish Hospital of St. Louis, Departments of Medicine and of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO, USA

› Institutsangaben

Abstract

als PDF herunterladen

Summary

The current system for the diagnosis and classification of von Willebrand disease (vWD) is quite complex, with more than 20 distinct variants described. Over the past few years considerable progress has been made toward an understanding of vWD at the molecular level. A small cluster of mutations within the vWF A1 homologous repeat appears responsible for over 90% of type IIB vWD. A similar cluster of mutations in the vWF A2 homologous repeat accounts for the majority of type II A vWD. By RFLP analysis, several type II vWD mutations have been shown to be recurrent on distinct haplotype backgrounds, suggesting independent genetic origins (see accompanying manuscript for a complete list of known polymorphisms). Several mutations at the N-terminus of the mature vWF subunit have been identified in association with abnormal factor VIII binding. Homozygotes for this abnormal vWF present with a hemophilia-like phenotype that is autosomal recessive in inheritance. In a small subset of patients with type III vWD large gene deletions have been identified on one or both vWF alleles. Carriers heterozygous for a deleted locus and one normal vWF gene are generally asymptomatic. Nonsense mutations and other defects resulting in loss of vWF mRNA expression from one allele have also been associated with a recessive type III vWD phenotype. No distinct molecular defect responsible for classic type I vWD has yet been defined.

PDF (1472 kb)

Referenzen

References
1 Lyons SE, Bruck ME, Bowie EJW, Ginsburg D. Impaired intracellular transport produced by a subset of type II A von Willebrand disease mutations. J Biol Chem 1992; 267: 4424-4430
2 Cooney KA, Nichols WC, Bruck ME, Bahou WF, Shapiro AD, Bowie EJW, Gralnick HR, Ginsburg D. The molecular defect in type II B von Willebrand disease. Identification of four potential missense mutations within the putative GpIb binding domain. J Clin Invest 1991; 87: 1227-1233
3 Randi AM, Rabinowitz I, Mancuso DJ, Mannucci PM, Sadler JE. Molecular basis of von Willebrand disease type II B. Candidate mutations cluster in one disulfide loop between proposed platelet glycoprotein Ib binding sequences. J Clin Invest 1991; 87: 1220-1226
4 Murray EW, Giles AR, Lillicrap D. Germ-line mosaicism for a valine-to-methionine substitution at residue 553 in the glycoprotein Ib-binding domain of von Willebrand factor, causing type II B von Willebrand disease. Am J Hum Genet 1992; 50: 199-207
5 Cooney KA, Lyons SE, Ginsburg D. Functional analysis of a type II B von Willebrand disease missense mutation: Increased binding of large von Willebrand factor multimers to platelets. Proc Natl Acad Sci USA 1992; 89: 2869-2872
6 Kroner PA, Kluessendorf ML, Scott JP, Montgomery RR. Expressed full-length von Willebrand factor containing missense mutations linked to type II B von Willebrand disease shows enhanced binding to platelets. Blood 1992; 79: 2048-2055
7 Ware J, Dent JA, Azuma H, Sugimoto M, Kyrie PA, Yoshioka A, Ruggeri ZM. Identification of a point mutation in type II B von Willebrand disease illustrating the regulation of von Willebrand factor affinity for the platelet membrane glycoprotein Ib-IX receptor. Proc Natl Acad Sci USA 1991; 88: 2946-2950
8 Ginsburg D, Konkle BA, Gill JC, Montgomery RR, Bockenstedt PL, Johnson TA, Yang AY. Molecular basis of human von Willebrand disease: analysis of platelet von Willebrand factor mRNA. Proc Natl Acad Sci USA 1989; 86: 3723-3727
9 Chang H-Y, Chen Y-P, Chediak JR, Levene RB, Lynch DC. Molecular analysis of von Willebrand factor produced by endothelial cell strains from patients with type IIA von Willebrand disease. Blood 1989; 74 (Suppl. 01) 482a (Abstract)
10 Tuley EA, Gaucher C, Jorieux S, Worrall NK, Sadler JE, Mazurier C. Expression of von Willebrand factor “Normandy”: An autosomal mutation that mimics hemophilia A. Proc Natl Acad Sci USA 1991; 88: 6377-6381
11 Cacheris PM, Nichols WC, Ginsburg D. Molecular characterization of a unique von Willebrand disease variant. A novel mutation affecting von Willebrand factor/factor VIII interaction. J Biol Chem 1991; 266: 13499-13502
12 Kroner PA, Friedman KD, Fahs SA, Scott JP, Montgomery RR. Abnormal binding of factor VIII is linked with the substitution of glutamine for arginine 91 in von Willebrand factor in a variant form of von Willebrand disease. J Biol Chem 1991; 266: 19146-19149
13 Jorieux S, Tuley EA, Gaucher C, Mazurier C, Sadler JE. The mutation Arg (53) → Trp causes von Willebrand disease Normandy by abolishing binding to factor VIII. Studies with recombinant von Willebrand factor. Blood 1992; 79: 563-567
14 Rodeghiero F, Castaman G, Dini E. Epidemiological investigation of the prevalence of von Willebrand’s disease. Blood 1987; 69: 454-459
15 Miller CH, Lenzi R, Breen C. Prevalence of von Willebrand’s disease among U.S. adults. Blood 1987; 70 (Suppl. 01) 377
16 Kitchin PA, Szotyori Z, Fromholc C, Almond N. Avoidance of false positives. Nature 1990; 344: 201
17 Shuldiner AR, Nirula A, Roth J. Hybrid DNA artifact from PCR of closely related target sequences. Nucleic Acids Res 1989; 17: 4409
18 Meyerhans A, Vartanian J-P, Wain-Hobson S. DNA recombination during PCR. Nucleic Acids Res 1990; 18: 1687-1961
19 Bonthron DR, Orr EC, Mitsock LM, Ginsburg D, Handin RI, Orkin SH. Nucleotide sequence of pre-pro-von Willebrand factor cDNA. Nucleid Acids Res 1986; 14: 7125-7127
20 Shelton-Inloes BB, Titani K, Sadler E. cDNA sequences for human von Willebrand factor reveal five types of repeated domains and five possible protein sequence polymorphisms. Biochemistry 1986; 25: 3164-3171
21 Verweij CL, Diergaarde PJ, Hart M, Pannekoek H. Full-length von Willebrand factor (vWF) cDNA encodes a highly repetitive protein considerably larger than the mature vWF subunit. EMBO J 1986; 5: 1839-1847
22 Berkowitz SD, Ruggeri ZN, Zimmerman TS. Von Willebrand disease. In: Coagulation and Bleeding Disorders. The Role of Factor VIII and von Willebrand Factor. Zimmerman TS, Ruggeri ZM. (eds) New York: Marcel Dekker, Inc.; 1989: 215-259
23 Bloom AL. Von Willebrand factor: clinical features of inherited and acquired disorders. Mayo Clin Proc 1991; 66: 743-751
24 Holmberg L, Nilsson IM. Von Willebrand disease. Clin Haematol 1985; 14: 461-488
25 Bahnak BR, Lavergne J-M, Rothschild C, Meyer D. A stop codon in a patient with severe, type III, von Willebrand disease. Blood 1991; 78: 1148-1149
26 Eikenboom JCJ, Briët E, Reitsma PH, Ploos van Amstel HK. Severe type III von Willebrand’s disease in the Dutch population is often associated with the absence of von Willebrand factor messenger RNA. Thromb Haemostas 1991; 65: 1127 (Abstract)
27 Zhang ZP, Falk G, Blombäck M, Egberg N, Anvret M. Identification of a new nonsense mutation in the von Willebrand factor gene in patients with von Willebrand disease type III. Hum Mol Genet 1992; 1: 61-62
28 Shelton-Inloes BB, Chehab FF, Mannucci PM, Federici AB, Sadler JE. Gene deletions correlate with the development of alloantibodies in von Willebrand Disease. J Clin Invest 1987; 79: 1459-1465
29 Ngo KY, Glotz VT, Koziol JA, Lynch DC, Gitschier J, Ranieri P, Ciavarella N, Ruggeri ZM, Zimmerman TS. Homozygous and heterozygous deletions of the von Willebrand factor gene in patients and carriers of severe von Willebrand disease. Proc Natl Acad Sci USA 1988; 85: 2753-2757
30 Peake IR, Liddell MB, Moodie P, Standen G, Mancuso DJ, Tuley EA, Westfield LA, Sorace JM, Sadler JE, Verweij CL, Bloom AL. Severe type III von Willebrand’s disease caused by deletion of Exon 42 of the von Willebrand factor gene: family studies that identify carriers of the condition and a compound heterozygous individual. Blood 1990; 75: 654-661
31 Nichols WC, Lysons SE, Harrison JS, Cody RL, Ginsburg D. Severe von Willebrand disease due to a defect at the level of von Willebrand factor mRNA expression: detection by exonic PCR-restriction fragment length polymorphism analysis. Proc Natl Acad Sci USA 1991; 88: 3857-3861
32 Berkowitz SD, Dent J, Roberts J, Fujimura Y, Plow EF, Titani K, Ruggeri ZM, Zimmerman TS. Epitope mapping of the von Willebrand factor subunit distinguishes fragments present in normal and type IIA von Willebrand Disease from those generated by plasmin. J Clin Invest 1987; 79: 524-531
33 Weiss HJ, Pietu G, Rabinowitz R, Girma J-P, Rogers J, Meyer D. Heterogeneous abnormalities in the multimeric structure, antigenic properties, and plasma-platelet content of factor VIII/von Willebrand factor in subtypes of classic (type I) and variant (type II A) von Willebrand’s disease. J Lab Clin Med 1983; 101: 411-425
34 Batlle J, Lopez FernandezMF, Campos M, Justica B, Berges C, Nacarro JL, Diaz CremadesJM, Kasper CK, Dent JA, Ruggeri ZM, Zimmerman TS. The heterogeneity of type IIA von Willebrand’s disease: studies with protease inhibitors. Blood 1986; 68: 1207-1212
35 Gralnick HR, Williams SB, McKeown LP, Maisonneuve P, Jenneau C, Sultan Y, Rick ME. In vitro correction of the abnormal multimeric structure of von Willebrand factor in type IIA von Willebrand’s disease. Proc Natl Acad Sci USA 1985; 82: 5968-5972
36 Zimmerman TS, Dent JA, Ruggeri ZM, Hannini LH. Subunit composition of plasma von Willebrand factor. J Clin Invest 1986; 77: 947-951
37 Kunicki TJ, Montgomery RR, Schullek J. Cleavage of human von Willebrand factor by platelet calcium-activated protease. Blood 1985; 65: 352-356
38 Dent JA, Galbusera M, Ruggeri ZM. Heterogeneity of plasma von Willebrand factor multimers resulting from proteolysis of the constituent subunit. J Clin Invest 1991; 88: 774-782
39 Dent JA, Berkowitz SD, Ware J, Kasper CK, Ruggeri ZM. Identification of a cleavage site directing the immunochemical detection of molecular abnormalities in type IIA von Willebrand factor. Proc Natl Acad Sci USA 1990; 87: 6306-6310
40 Barker D, Schafer M, White R. Restriction sites containing CpG show a higher frequency of polymorphism in human DNA. Cell 1984; 36: 131-138
41 Sadler JE. Von Willebrand factor. J Biol Chem 1991; 266: 22777-22780
42 Ginsburg D, Bowie EJW. Molecular genetics of von Willebrand disease. Blood 1992; 79: 2507-2519
43 Mazurier C, Diéval J, Jorieux S, Delobel J, Goudemand M. A new von Willebrand factor (vWF) defect in a patient with factor VIII (FVIII) deficiency but with normal levels and multimeric patterns of both plasma and platelet vWF. Characterization of abnormal vWF/ FVIII interaction. Blood 1990; 75: 20-26
44 Nishino M, Girma J-P, Rothschild C, Fressinaud E, Meyer D. New variant of von Willebrand disease with defective binding to factor VIII. Blood 1989; 74: 1591-1599
45 Mazurier C, Gaucher C, Jorieux S, Parquet-Gernez A, Goudemand M. Evidence for a von Willebrand factor defect in factor VIII binding in three members of a family previously misdiagnosed mild haemophilia A and haemophilia A carriers: consequences for therapy and genetic counselling. Br J Haematol 1990; 76: 372-379
46 Gaucher C, Jorieux S, Mercier B, Oufkir D, Mazurier C. The “Normandy” variant of von Willebrand disease: Characterization of a point mutation in the von Willebrand factor gene. Blood 1991; 77: 1937-1941
47 Gaucher C, Mercier B, Jorieux S, Oufkir D, Mazurier C. Identification of two point mutations in the von Willebrand factor gene of three families with the “Normandy” variant of von Willebrand disease. Br J Haematol 1991; 78: 506-514
48 Kroner PA, Fahs SA, Vokac EA, Friedman KD, Montgomery RR. Novel missense mutations in von Willebrand factor (vWF) associated with defective vWF/factor VIII interaction in a patient with type I von Willebrand disease. Blood 1991; 78 (Suppl. 01) 1278a (Abstract)
49 Peerlinck K, Eikenboom JCJ, Ploos van AmstelHK, Sangtawesin W, Arnout J, Reitsma PH, Vermylen J, Briët E. A patient with von Willebrand’s disease characterized by a compound heterozygosity for a substiution of Arg⁸⁵⁴ by Gin in the putative factor-VIII-binding domain of von Willebrand factor (vWF) on one allele and very low levels of mRNA from the second vWF allele. Br J Haematol 1992; 80: 358-363
50 Rabinowitz I, Tuley EA, Mancuso DJ, Randi AM, Firkin BG, Howard MA, Sadler JE. A missense mutation selectively abolishes ristocetin-induced von Willebrand factor binding to platelet glycoprotein lb. Proc Natl Acad Sci USA. 1992 in press
51 Mancuso DJ, Montgomery RR, Adam P. The identification of a candidate mutation in the von Willebrand factor gene of patients with a variant form of Type I von Willebrand disease. Blood 1991; 78 (Suppl. 01) 67a (Abstract)
52 Miller JL, Cunningham D, Lyle VA, Finch CN. Mutation in the gene encoding the α chain of platelet glycoprotein Ib in platelet-type von Willebrand disease. Proc Natl Acad Sci USA 1991; 88: 4761-4765
53 Russell SD, Roth GJ. A mutation in the platelet glyoprotein (GP) Ib alpha gene associated with pseudo-von Willebrand disease. Blood 1991; 1114: 281a (Abstract)
54 Lavergne JM, Ribba AS, Bahnak BR, de Pailette L, Derlon A, Meyer D, Piétu G. The use of denaturing gradient gel electrophoresis to detect base change in the von Willebrand factor gene from type IIA von Willebrand disease patients. Thromb Haemostas 1991; 65: 738 (Abstract)
55 Inbal A, Seligsohn U, Kornbrot N, Brenner B, Harrison P, Randi A, Rabinowitz I, Sadler JE. Characterization of three mutations causing von Willebrand disease type IIA in five unrelated families. Thromb Haemostas 1992; 67: 618-622
56 Sugiura I, Matsushita T, Tanimoto M, Takahashi I, Yamazaki T, Yamamoto K, Takamatsu J, Kamiya T, Saito H. Three distinct point mutations of the von Willebrand factor gene in four patients with type IIA von Willebrand disease. Thromb Haemostas 1992; 67: 612-617
57 Gaucher C, Hanss M, Dechavanne M, Mazurier C. Substitution of Cysteine for Phenylalanine 751 in mature von Willebrand factor is a novel candidate mutation in a family with type IIA von Willebrand disease. Br J Haematol. 1992 in press
58 Bowen DJ, Standen GR, Bignell P, Peake IR. A C → T transition in the gene for von Willebrand factor effects the replacement of ARG 1597 (CGG) with TRP (TGG) in affected members of a family with type IIA von Willebrand’s disease. Br J Haematol 1990; 76 (Suppl. 01) 36 (Abstract)
59 Iannuzzi MC, Hidaka N, Boehnke ML, Bruck ME, Hanna WT, Collins FS, Ginsburg D. Analysis of the relationship of von Willebrand disease (vWD) and hereditary hemorrhagic telangiectasia and identification of a potential type IIA vWD mutation (Ile865 to Thr). Am J Hum Genet 1991; 48: 757-763
60 Ribba AS, Lavergne JM, Bahnak BR, Derlon A, Piétu G, Meyer D. Duplicaton of a methionine within the glycoprotein Ib binding domain of von Willebrand factor detected by denaturing gradient gel electrophoresis in a patient with type IIB von Willebrand disease. Blood 1991; 78: 1738-1743
61 Murray EW, Giles AR, Lillicrap D. Recurring mutations at CpG dinucleotides and germ line mosaicism in the von Willebrand factor (vWF) gene as a cause of type IIB von Willebrand’s disease (vWD). Am J Hum Genet 1991; 49 (04) 199 (Abstract)
62 Sugiura I, Matsushita T, Tanimoto M, Takamatsu J, Kamiya T, Saito H, Furuya H, Kato Y. The molecular defects in Japanese patients with type II von Willebrand disease. Thromb Haemostas 1991; 65: 763 (Abstract)
63 Holmberg L, Donner M, Dahlbäck B, Nilsson IM. Apparently recessive IIB von Willebrand disease (vWD) is causes by de novo mutations (ARG543 → TRP; VAL551 → LEU). Blood 1991; 78 (Suppl. 01) 150a (Abstract)
64 Donner M, Andersson AM, Kristoffersson AC, Nilsson IM, Dahlbäck B, Holmberg L. An Arg545----Cys545 substitution mutation of the von Willebrand factor in type IIB von Willebrand’s disease. Eur J Haematol 1991; 47: 342-345
65 Randi AM, Tuley EA, Jorieux S, Rabinowitz I, Sadler JE. A missense mutation (R578Q) in von Willebrand disease (vWD) type IIB affects von Willebrand factor (vWF) binding to GPIb but not to collagen or heparin: studies with recombinant vWF. Blood 1991; 78 (Suppl. 01) 179a (Abstract)
66 Randi AM, Jorieux S, Tuley EA, Mazurier C, Sadler JE. Recombinant von Willebrand factor Arg(578) → Gln: A type IIB von Willebrand disease mutation affects binding to glycoprotein Ib but not to collagen or heparin. J Biol Chem. 1992 in press
67 Wise RJ, Ewenstein BM, Narins SC, Gorlin J, Jesson MI, Handin RI. Autosomal recessive transmission of the Hemophilia A phenotype due to a von Willebrand factor point mutation. Blood 1991; 78 (Suppl. 01) 67a (Abstract)
68 Bernardi F, Marchetti G, Guerra S, Casonato A, Gemmati D, Patracchini P, Ballerini G, Conconi F. A de novo and heterozygous gene deletion causing a variant of von Willebrand disease. Blood 1990; 75: 677-683