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Thromb Haemost 1995; 74(01): 161-166
DOI: 10.1055/s-0038-1642670
Symposium
Von Willebrand Disease and Factor
Schattauer GmbH Stuttgart

Molecular Mechanism and Classification of von Willebrand Disease

J Evan Sadler
Howard Hughes Medical Institute, Departments of Medicine and Biochemistry and Molecular Biophysics, The Jewish Hospital of St. Louis, Washington University School of Medicine, St. Louis, MO 63110, USA
,
Tadashi Matsushita
Howard Hughes Medical Institute, Departments of Medicine and Biochemistry and Molecular Biophysics, The Jewish Hospital of St. Louis, Washington University School of Medicine, St. Louis, MO 63110, USA
,
Zhengyu Dong
Howard Hughes Medical Institute, Departments of Medicine and Biochemistry and Molecular Biophysics, The Jewish Hospital of St. Louis, Washington University School of Medicine, St. Louis, MO 63110, USA
,
Elodee A Tuley
Howard Hughes Medical Institute, Departments of Medicine and Biochemistry and Molecular Biophysics, The Jewish Hospital of St. Louis, Washington University School of Medicine, St. Louis, MO 63110, USA
,
Lisa A Westfield
Howard Hughes Medical Institute, Departments of Medicine and Biochemistry and Molecular Biophysics, The Jewish Hospital of St. Louis, Washington University School of Medicine, St. Louis, MO 63110, USA
› Author Affiliations
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Publication History

Publication Date:
09 July 2018 (online)

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  • References

  • 1 Nilsson IM, Blombäck M, Jorpes E, Blombäck B, Johansson S-A. v. Willebrand’s disease and its correction with human plasma fraction 1-0. Acta Med Scand 1957; 159: 179-188
    PubMedGoogle Scholar
  • 2 Bouma BN, Wiegerinck Y, Sixma JJ, van Mourik JA, Mochtar IA. Immunological characterization of purified anti-haemophilic factor A (factor VIII) which corrects abnormal platelet retention in von Willebrand’s disease. Nature New Biol 1972; 236: 104-106
    CrossrefPubMedGoogle Scholar
  • 3 Holmberg L, Nilsson IM. Genetic variants of von Willebrand’s disease. Br Med J 1972; 3: 317-320
    CrossrefPubMedGoogle Scholar
  • 4 Hoyer LW, Shainoff JR. Factor VIII-related protein circulates in normal human plasma as high molecular weight multimers. Blood 1980; 55: 1056-1059
    PubMedGoogle Scholar
  • 5 Ruggeri ZM, Zimmerman TS. Variant von Willebrand’s disease. Characterization of two subtypes by analysis of multimeric composition of factor VIII/von Willebrand factor in plasma and platelets J Clin Invest 1980; 65: 1318-1325
    CrossrefPubMedGoogle Scholar
  • 6 Ruggeri ZM, Pareti FI, Mannucci PM, Ciavarella N, Zimmerman TS. Heightened interaction between platelets and factor VIII/von Willebrand factor in a new subtype of von Willebrand’s disease. N Engl J Med 1980; 302: 1047-1051
    CrossrefPubMedGoogle Scholar
  • 7 Sadler JE, Shelton-Inloes BB, Sorace JM, Harlan JM, Titani K, Davie EW. Cloning and characterization of two cDNAs coding for human von Willebrand factor. Proc Natl Acad Sci USA 1985; 82: 6394-6398
    CrossrefPubMedGoogle Scholar
  • 8 Lynch DC, Zimmerman TS, Collins CJ, Brown M, Morin MJ, Ling EH, Livingston DM. Molecular cloning of cDNA for human von Willebrand factor: authentication by a new method. Cell 1985; 41: 49-56
    CrossrefPubMedGoogle Scholar
  • 9 Ginsburg D, Handin RI, Bonthron DT, Donlon TA, Bruns G AP, Latt SA, Orkin SH. Human von Willebrand factor (vWF): isolation of complementary DNA (cDNA) clones and chromosomal localization. Science 1985; 228: 1401-1406
    CrossrefPubMedGoogle Scholar
  • 10 Verweij CL, de Vries CJ M, Distel B, van Zonneveld A-J, van Kessel AG, van Mourik JA, Pannekoek H. Construction of cDNA coding for human von Willebrand factor using antibody probes for colony-screening and mapping of the chromosomal gene. Nucleic Acids Res 1985; 13: 4699-4717
    CrossrefPubMedGoogle Scholar
  • 11 Shelton-Inloes BB, Chehab FF, Mannucci PM, Federici AB, Sadler IE. Gene deletions correlate with the development of alloantibodies in von Willebrand diseases. J Clin Invest 1987; 79: 1459-1465
    CrossrefPubMedGoogle Scholar
  • 12 Ngo K-Y, Glotz VT, Koziol JA, Lynch DC, Gitschier J, Ranieri RP, Ciavarella N, Ruggeri ZM, Zimmerman TS. Homozygous and heterozygous deletions of the von Willebrand factor gene in patients and carriers of severe von Willebrand’s disease. Proc Natl Acad Sci USA 1988; 85: 2753-2757
    CrossrefPubMedGoogle Scholar
  • 13 Sadler JE. A revised classification of von Willebrand disease. Thromb Haemost 1994; 71: 520-525
    Article in Thieme ConnectPubMedGoogle Scholar
  • 14 Sadler JE, Gralnick HR. Commentary: a new classification of von Willebrand disease. Blood 1994; 84: 676-679
    PubMedGoogle Scholar
  • 15 Zhang ZP, Blömback M, Nyman D, Anvret M. Mutations of von Willebrand factor gene in families with von Willebrand disease in the Aland Islands. Proc Natl Acad Sci USA 1993; 90: 7937-7940
    CrossrefPubMedGoogle Scholar
  • 16 Ginsburg D, Sadler JE. von Willebrand disease: a database of point mutations, insertions, and deletions. Thromb Haemost 1993; 69: 177-184
    Article in Thieme ConnectPubMedGoogle Scholar
  • 17 Foster PA, Fulcher CA, Marti T, Titani K, Zimmerman TS. A major factor VIII binding domain resides within the amino-terminal 272 amino acid residues of von Willebrand factor. J Biol Chem 1987; 262: 8443-8446
    CrossrefPubMedGoogle Scholar
  • 18 Sadler JE, Davie EW, Hemophilia A, Hemophilia B. and von Willebrand Disease In: The Molecular Basis of Blood Diseases. 2nd ed. Stamatoyannopoulos G, Nienhuis AW, Majerus PW, Varmus H. (eds). Saunders WB. Co. Philadelphia: 1994. pp 657-700
  • 19 Nishino M, Girma J-P, Rothschild C, Fressinaud E, Meyer D. New variant of von Willebrand disease with defective binding to factor Vm. Blood 1989; 74: 1591-1599
    CrossrefPubMedGoogle Scholar
  • 20 Mazurier C, Dieval 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
    CrossrefPubMedGoogle Scholar
  • 21 Mazurier C. von Willebrand disease masquerading as haemophilia A. Thromb Haemost 1992; 67: 391-396
    Article in Thieme ConnectPubMedGoogle Scholar
  • 22 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 (Suppl. 01) a 178-178
    PubMedGoogle Scholar
  • 23 Rick ME, Krizek DM. Identification of a molecular defect in a patient with von Willebrand’s disease and defective binding of factor VIE. Blood 1994; 84 Suppl (Suppl. 01) a 59-59
    PubMedGoogle Scholar
  • 24 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
    CrossrefPubMedGoogle Scholar
  • 25 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
    CrossrefPubMedGoogle Scholar
  • 26 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
    CrossrefPubMedGoogle Scholar
  • 27 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
    PubMedGoogle Scholar
  • 28 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
    PubMedGoogle Scholar
  • 29 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
    PubMedGoogle Scholar
  • 30 Mazurier C, Gaucher C, Jorieux S, Parquet GA, 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
    CrossrefPubMedGoogle Scholar
  • 31 Mazurier C, Gaucher C, Jorieux S, Goudemand M. the Collaborative Group: Biological effect of desmopressin in eight patients with type 2N (‘Normandy’) von Willebrand disease. Br J Haematol 1994; 88: 849-854
    CrossrefPubMedGoogle Scholar
  • 32 Lopez-Fernandez MF, Blanco-Lopez MJ, Castineira MP, Batlle J. Further evidence for recessive inheritance of von Willebrand disease with abnormal binding of von Willebrand factor to factor VIII. Am J Hematol 1992; 40: 20-27
    CrossrefPubMedGoogle Scholar
  • 33 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 (Suppl. 01) a 67-67
    PubMedGoogle Scholar
  • 34 Rabinowitz I, Tuley EA, Mancuso DJ, Randi AM, Firkin BG, Howard MA, Sadler JE. von Willebrand disease type B: a missense mutation selectively abolishes ristocetin-induced von Willebrand factor binding to platelet glycoprotein lb. Proc Natl Acad Sci USA 1992; 89: 9846-9849
    CrossrefPubMedGoogle Scholar
  • 35 Matsushita T, Sadler JE. Alanine scanning mutagenesis of the A1 domain of human von Willebrand factor identifies amino acid residues essential for normal binding to platelet glycoprotein lb. Blood 1994; 84 Suppl (Suppl. 01) a 387-387
    PubMedGoogle Scholar
  • 36 Lyons SE, Bruck ME, Bowie EJ W, Ginsburg D. Impaired intracellular transport produced by a subset of type IIA von Willebrand disease mutations. J Biol Chem 1992; 267: 4424-4430
    PubMedGoogle Scholar
  • 37 Gaucher C, Dieval J, Mazurier C. Characterization of von Willebrand factor gene defects in two unrelated patients with type IIC von Willebrand disease. Blood 1994; 84: 1024-1030
    PubMedGoogle Scholar
  • 38 Verweij CL, Hart M, Pannekoek H. Expression of variant von Willebrand factor (vWF) cDNA in heterologous cells: requirement of the pro-polypeptide in vWF multimer formation. EMBO J 1987; 6: 2885-2890
    PubMedGoogle Scholar
  • 39 Wise RJ, Pittman DD, Handin RI, Kaufman RJ, Orkin SH. The propeptide of von Willebrand factor independently mediates the assembly of von Willebrand multimers. Cell 1988; 52: 229-236
    CrossrefPubMedGoogle Scholar
  • 40 Mayadas TN, Wagner DD. In vitro multimerization of von Willebrand factor is triggered by low pH. Importance of the propolypeptide and free sulfhydryls J Biol Chem 1989; 264: 13497-13503
    CrossrefPubMedGoogle Scholar
  • 41 Mayadas TN, Wagner DD. Vicinal cysteines in the prosequence play a role in von Willebrand factor multimer assembly. Proc Natl Acad Sci USA 1992; 89: 3531-3535
    CrossrefPubMedGoogle Scholar
  • 42 Holmberg L, Dent JA, Schneppenheim R, Budde U, Ware J, Ruggeri ZM. von Willebrand factor mutation enhancing interaction with platelets in patients with normal multimeric structure. J Clin Invest 1993; 91: 2169-2177
    CrossrefPubMedGoogle Scholar
  • 43 Ribba AS, Christophe O, Derlon A, Cherel G, Siguret V, Lavergne JM, Girma JP, Meyer D, Pietu G. Discrepancy between IIA phenotype and IIB genotype in a patient with a variant of von Willebrand disease. Blood 1994; 83: 833-841
    PubMedGoogle Scholar
  • 44 Rabinowitz I, Randi AM, Shindler KS, Tuley EA, Rustagi PK, Sadler JE. Type IIB mutation His-505→Asp implicates a new segment in the control of von Willebrand factor binding to platelet glycoprotein lb. J Biol Chem 1993; 268: 20497-20501
    PubMedGoogle Scholar
  • 45 Christophe O, Ribba AS, Baruch D, Obert B, Rouault C, Niinomi K, Pietu G, Meyer D, Girma JP. Influence of mutations and size of multimers in type II von Willebrand disease upon the function of von Willebrand factor. Blood 1994; 83: 3553-3561
    PubMedGoogle Scholar
  • 46 Cooney KA, Lyons SE, Ginsburg D. Functional analysis of a type IIB von Willebrand disease missense mutation: Increased binding of large von Willebrand factor multimers to platelets. Proc Natl Acad Sci USA 1992; 89: 2869-2872
    CrossrefPubMedGoogle Scholar
  • 47 Inbal A, Kornbrot N, Harrison P, Randi AM, Sadler IE. Effect of type IIB von Willebrand disease mutation Arg(545)Cys on platelet glycoprotein lb binding - studies with recombinant von Willebrand factor. Thromb Haemost 1993; 70: 1058-1062
    Article in Thieme ConnectPubMedGoogle Scholar
  • 48 Ware J, Dent JA, Azuma H, Sugimoto M, Kyrle PA, Yoshioka A, Ruggeri ZM. Identification of a point mutation in type IIB 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
    CrossrefPubMedGoogle Scholar
  • 49 Kroner PA, Kluessendorf ML, Scott JP, Montgomery RR. Expressed full-length von Willebrand factor containing missense mutations linked to type IIB von Willebrand disease shows enhanced binding to platelets. Blood 1992; 79: 2048-2055
    PubMedGoogle Scholar
  • 50 Randi AM, Jorieux S, Tuley EA, Mazurier C, Sadler JE. Recombinant von Willebrand factor Arg578→Gln. A type IIB von Willebrand disease mutation affects binding to glycoprotein lb but not to collagen or heparin. J Biol Chem 1992; 267: 21187-21192
    PubMedGoogle Scholar
  • 51 Hilbert L, Gaucher C, de Romeuf C, Horellou M-H, Vink T, Mazurier C. Leu697→Val mutation in mature von Willebrand factor is responsible for type IIB von Willebrand disease. Blood 1994; 83: 1542-1550
    PubMedGoogle Scholar
  • 52 Rodeghiero F, Castaman G, Dini E. Epidemiological investigation of the prevalence of von Willebrand’s disease. Blood 1987; 69: 454-459
    PubMedGoogle Scholar
  • 53 Blombäck M, Eneroth P, Andersson O, Anvret M. On laboratory problems in diagnosing mild von Willebrand’s disease. Am J Hematol 1992; 40: 117-120
    CrossrefPubMedGoogle Scholar
  • 54 Sadler IE, Ginsburg D. A database of polymorphisms in the von Willebrand factor gene and pseudogene. Thromb Haemost 1993; 69: 185-191
    Article in Thieme ConnectPubMedGoogle Scholar
  • 55 Gill JC, Endres-Brooks J, Bauer PJ, Marks WJ, Montgomery RR. The effect of ABO blood group on the diagnosis of von Willebrand disease. Blood 1987; 69: 1691-1695
    CrossrefPubMedGoogle Scholar
  • 56 Orstavik KH, Kornstad L, Reisner H, Berg K. Possible effect of Secretor locus on plasma concentration of factor VIII and von Willebrand factor. Blood 1989; 73: 990-993
    PubMedGoogle Scholar
  • 57 Zhang ZP, Lindstedt M, Falk G, Blombäck M, Egberg N, Anvret M. Nonsense mutations of the von Willebrand factor gene in patients with von Willebrand disease type III and type I. Am J Hum Gene 1992; 51: 850-858
    PubMedGoogle Scholar
  • 58 Zhang ZP, Blombäck M, Egberg N, Falk G, Anvret M. Characterization of the von Willebrand factor gene (vWF) in von Willebrand disease type III patients from 24 families of Swedish and Finnish origin. Genomics 1994; 21: 188-193
    CrossrefPubMedGoogle Scholar
  • 59 Schneppenheim R, Krey S, Bergmann F, Bock D, Budde U, Lange M, Linde R, Mittler U, Meili E, Mertes G, Olek K, Plendl H, Simeoni E. Genetic heterogeneity of severe von Willebrand disease type III in the German population. Hum Genet 1994; 94: 640-652
    PubMedGoogle Scholar
  • 60 Eikenboom IC, Reitsma PH, Peerlinck KM J, Briet E. Recessive inheritance of von Willebrand’s disease type I. Lancet 1993; 341: 982-986
    CrossrefPubMedGoogle Scholar
  • 61 Eikenboom JC J, Reitsma PH, Castaman G, Tuley EA, Briet E, Sadler JE. Dominant type 1 von Willebrand disease associated with mutated cysteine residues in the D3 domain of von Willebrand factor. Thromb Haemost. 1995 in press
    PubMedGoogle Scholar