Skip to main content
SpringerLink
Log in

Molecular Biology of the Various Types of von Willebrand Disease

  • Chapter
Hereditary Diseases and Blood Transfusion

Part of the book series: Developments in Hematology and Immunology ((DIHI,volume 30))

  • 42 Accesses

Abstract

Historically discovered in 1926 by Erik von Willebrand studying bleeding patients living on an island of the Ă…land archipelago, von Willebrand disease (vWD) is now recognised as the most common inherited bleeding disorder. It defines a heterogeneous group of patients with quantitative or qualitative defects of the von Willebrand factor (vWF) [1] which is a large glycoprotein present in plasma, subendothelium and the alpha granules of platelets. Synthesized exclusively by both endothelial cells and megakaryocytes, vWF plays a dual role in haemostasis. It mediates platelet adhesion to the subendothelium at the site of vessel injury and its circulating form carries and stabilizes factor VIII (FVIII), [2].

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Ruggeri ZM, Zimmerman TS. Classification of von Willebrand disease. J Clin Lab Anal 1987;1:353–62.

    Article  CAS  Google Scholar 

  2. Ruggeri ZM, War J. Von Willebrand factor. FASEB Journal 1993;7:308–16.

    PubMed  CAS  Google Scholar 

  3. Ginsburg D, Handin RI, Bonthron, et al. Human von Willebrand factor (vWF): Isolation of complementary DNA (cDNA) clones and chromosomal localization. Science 1985;228:1401–06.

    Article  PubMed  CAS  Google Scholar 

  4. Lynch DC, Zimmerman TS, Collins CJ, Brown M, Morin MJ, Ling EH. Molecular cloning of cDNA for human von Willebrand factor: Authentification by a new method. Cell 1985;41:49–56.

    Article  PubMed  CAS  Google Scholar 

  5. 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 Nat Acad Sci USA 1985;82:6394–98.

    Article  PubMed  CAS  Google Scholar 

  6. Verweij CL, de Vries CJM, Distel B, et al. 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;13:4699–717.

    Article  PubMed  CAS  Google Scholar 

  7. Verweij CL, Diergaarde PJ, Hart M, Pannekoek H. Full-length von Willebrand factor (vWF) cDNA encodes a highly repetitive protein larger than the mature vWF subunit. EMBO J 1986;5:1839–47.

    PubMed  CAS  Google Scholar 

  8. Patracchini P, Calzolari E, Aiello V, et al. Sublocalization of von Willebrand factor pseudogene to 22q11.22-q11.23 by in situ hybridization in a 46, X, t (X;22) (pter;q11.21) translocation. Hum Genet 1989;83:264–66.

    Article  PubMed  CAS  Google Scholar 

  9. Mancuso DJ, Tuley EA, Westfield LA, et al. Human von Willebrand factor gene and pseudogene. Structural analysis and differentiation by polymerase chain reaction. Biochemistry 1991;30:253–69.

    Article  PubMed  CAS  Google Scholar 

  10. Mancuso DJ, Tuley EA, Westfield LA, Worrall NK, Shelton-Inloes BB. Structure of the gene for human von Willebrand factor. J Biol Chem 1989;264: 19514–27.

    PubMed  CAS  Google Scholar 

  11. Sadler JE, Ginsburg D. A data base of polymorphisms in the von Willebrand factor gene and pseudogene. Thromb Haemost 1993;69:185–91.

    PubMed  CAS  Google Scholar 

  12. Sadler JE. A revised classification of von Willebrand disease. Thromb Haemost 1994; 71:520–25.

    PubMed  CAS  Google Scholar 

  13. Ginsburg D, Sadler JE. Von Willebrand disease: A database of point mutations, insertions and deletions. Thromb Haemost 1993;69:177–84.

    PubMed  CAS  Google Scholar 

  14. Mannucci PM, Bloom AL, Larrieu MJ,Nilsson IM, West RR. Atherosclerosis and von Willebrand factor. Prevalence of severe von Willebrand’s disease in western Europe and Israel. Br J Haematol 1984;57:163–69.

    PubMed  CAS  Google Scholar 

  15. 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;79:1459–65.

    Article  PubMed  CAS  Google Scholar 

  16. Ngo KV, Glotz VT, Koziol JA, et al. Homozygous and heterozygous deletions of the von Willebrand factor gene in patients and carriers of severe von Willebrand disease.Proc Nat Acad Sci USA 1988;85:2753–57.

    Article  PubMed  CAS  Google Scholar 

  17. Peake IR, Liddell MB, Moodie P, et 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;75:654–61.

    PubMed  CAS  Google Scholar 

  18. Mancuso DJ, Tuley EA, Castillo R, de Bosch N, Mannucci PM, Sadler JE. Characterization of partial gene deletions in type III von Willebrand disease with allo-antibody inhibitors. Thromb Haemost 1994;72:180–85.

    PubMed  CAS  Google Scholar 

  19. Anvret M, Blombäck M, Lindstedt M, Söderlind E, Tapperpersson M, Thelander AC. Genetic and blood coagulation characterization of Swedish families with von Willebrand’s disease type I and type III. New aspect of heredity. Hum Genet 1992;89: 147–54.

    Article  PubMed  CAS  Google Scholar 

  20. Nichols WC, Lyons SE, Harrison JS, Cody RL, Ginsburg D. Severe von Willebrand disease due to a defect at the level of von Willebrand factor messenger RNA expression. Detection by exonic PCR restriction fragment length polymorphism analysis. Proc Natl Acad Sci USA 1991;88:3857–61.

    Article  PubMed  CAS  Google Scholar 

  21. Eikenboom JCJ, Ploos van Amstel HK, Reitsma PH, Briët E. Mutations in severe, type III von Willebrand’s disease in the Dutch population: Candidate missense and nonsense mutations associated with reduced levels of von Willebrand factor messenger RNA. Thromb Haemost 1992;68:448–54.

    PubMed  CAS  Google Scholar 

  22. Eikenboom JCJ, Reitsma PH, Peerlinck KMJ, Briët E. Recessive inheritance of von Willebrand’s disease type I. Lancet 1993;341:982–86

    Article  PubMed  CAS  Google Scholar 

  23. Bahnak BR, Lavergne JM, Rothschild C, Meyer D. A stop codon in a patient with severe type III von Willebrand disease. Blood 1991;78:1148–49.

    PubMed  CAS  Google Scholar 

  24. Zhang ZP, Lindstedt M, Falk G, Blombäck M, Egberg N, Anvret M. Nonsens mutations of the von Willebrand factor gene in patients with von Willebrand disease type III and type I. Am J Hum Genet 1992;51:850–58.

    PubMed  CAS  Google Scholar 

  25. Zhang ZP, Falk G, Blombäck M, Egberg N, Anvret M. A single cytosine deletion in exon 18 of the von Willebrand factor gene is the most common mutation in Swedish vWD type III patients. Hum Mol Genet 1992;1:767–68

    Article  PubMed  CAS  Google Scholar 

  26. Zhang ZP, Blombäck M, Nyman D, Anvret M. Mutations of von Willebrand factor gene in families with von Willebrand disease in the Åland Islands. Proc Natl Acad Sci USA 1993;90:7937–40.

    Article  PubMed  CAS  Google Scholar 

  27. Wagner DD. Cell Biology of von Willebrand factor. Ann Rev Cell Biol 1990;6: 217–46.

    Article  PubMed  CAS  Google Scholar 

  28. Mayadas TN, Wagner DD. Vicinal cysteines in the prosequence play a role in von Willebrand factor multimer assembly. Proc Natl Acad Sci USA 1992;89:3531–35.

    Article  PubMed  CAS  Google Scholar 

  29. Dent JA, Galbusera M, Ruggeri ZM. Heterogeneity of plasma von Willebrand factor multimers resulting from proteolysis of the constituent subunit. J Clin Invest 1991; 88:774–82.

    Article  PubMed  CAS  Google Scholar 

  30. Berkowitz SD, Dent JA, Roberts JR, et al. Epitope mapping of the von Willebrand factor subunit distinguishes fragmets present in normal and type IIA von Willebrand disease from those generated by plasmin. J Clin Invest 1987; 79:524–31.

    Article  PubMed  CAS  Google Scholar 

  31. Dent JA, Ware J, Kasper CK, Ruggeri ZM, Berkowitz SD. Identification of a cleavage site directing the immunochemical detection of molecular abnormalities in type IIA von Willebrand factor. Proc. Natl Acad Sci USA 1990;87:6306–10.

    Article  PubMed  CAS  Google Scholar 

  32. Ginsburg D, Konkle BA, Gill JC, et al. Molecular basis of human von Willebrand disease: Analysis of platelet von Willebrand factor mRNA. Proc Natl Acad Sci USA 1989;86:3723–27.

    Article  PubMed  CAS  Google Scholar 

  33. Lyons SE, Bruck ME, Bowie EJW, Ginsburg D. Impaired intracellular transport produced by a subset of type IIA von Willebrand disease mutations. J Biol Chem 1992;267:4424–30.

    PubMed  CAS  Google Scholar 

  34. Gaucher C, Diéval J, Mazurier Cl. Characterization of von Willebrand factor gene defects in two urelated patients with type HC von Willebrand disease. Blood 1994; 84:1024–30.

    PubMed  CAS  Google Scholar 

  35. 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-Ib. J Biol Chem 1993; 268:20497–501.

    PubMed  CAS  Google Scholar 

  36. Hilbert L, Gaucher C, de Romeuf C, Horellou MH, Vink T, Mazurier C. Leu 697→Val mutation in mature von Willebrand factor is responsible for type IIB von Willebrand disease. Blood 1994;83:1542–50.

    PubMed  CAS  Google Scholar 

  37. Hölmberg L, Dent JA, Schneppenheim R, Budde U, Ware J, Ruggeri ZM. Von Wille-brand factor mutation enhancing interaction with platelets in patients with normal multimeric structure. J Clin Invest 1993;91:2169–77.

    Article  PubMed  Google Scholar 

  38. Howard MA, Salem HH, Thomas KB, et al. Variant von Willebrand’s disease type B. Revisited. Blood 1982;60:1420–28.

    PubMed  CAS  Google Scholar 

  39. Rabinowitz I, Tuley EA, Mancuso DJ, et al. Von Willebrand disease type B: A missense mutation selectively abolishes ristocetin-induced von Willebrand factor binding to platelet glycoprotein Ib. Proc Natl Acad Sci USA 1992;89: 9846–49.

    Article  PubMed  CAS  Google Scholar 

  40. Mazurier C, Diéval J, Jorieux S, Delobel J, Goudemand M. A new von Willebrand factor defect in a patient with factor VIII 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.

    PubMed  CAS  Google Scholar 

  41. Mazurier C. Von Willebrand disease masquerading as haemophilia A. Thromb Haemost 1992;67:391–96.

    PubMed  CAS  Google Scholar 

  42. Wise RJ, Ewenstein BM, Gorlin J, Narins SC, Jesson M, Handin RI. Autosomal recessive transmission of haemophilia A due to a von Willebrand factor mutation. Hum Genet 1993;91:367–72.

    Article  PubMed  CAS  Google Scholar 

  43. Siguret V, Lavergne J, Cherel G, et al. A novel case of compound heterozygosity with Normandy/type I von Willebrand disease (vWD). Direct demonstration of the segregation of one allele with a defective expression at the mRNA level causing type I vWD. Hum Genet 1994;93:95–102.

    Article  PubMed  CAS  Google Scholar 

  44. Eikenboom JC, Vink T, Briët E, Sixma JJ, Reitsma PH. Multiple substitutions in the von Willebrand factor gene that mimic the pseudogene sequence. Proc Natl Acad Sci USA 1994;91:2221–24.

    Article  PubMed  CAS  Google Scholar 

  45. Peake IR, Bowen D, Bignell P, et al. Family studies and prenatal diagnosis in severe von Willebrand disease by polymerase chain reaction amplification of a variable number tandem repeat region of the von Willebrand factor gene. Blood 1990;76: 555–61.

    PubMed  CAS  Google Scholar 

  46. Bignell P, Standen GR, Bowen DJ, Peake IR, Bloom AL. Rapid neonatal diagnosis of von Willebrand’s disease by use of the polymerase chain reaction. Lancet 1990; 336:638–39.

    Article  PubMed  CAS  Google Scholar 

  47. Ribba AS, Voorberg J, Meyer D, Pannekoek H, Pietu G. Characterization of recombinant von Willebrand factor corresponding to mutations in type IIA and type IIB von Willebrand disease. J Biol Chem 1992;267:23209–15.

    PubMed  CAS  Google Scholar 

  48. Pietu G, Ribba AS, de Paillette L, et al. Molecular study of von Willebrand disease: Identification of potential mutations in patients with type IIA and type IIB. Blood Coag Fibrin 1992;3:415–21.

    CAS  Google Scholar 

  49. Donner M, Kristoffersson AC, Berntorp E, et al. Two new candidate mutations in type IIA von Willebrand’s disease (Arg834→Gly, Gly846→Arg) and one polymorphism (Tyr821→Cys) in the A2 region of the von Willebrand factor. Eur J Haemat 1993; 51:38–44.

    Article  CAS  Google Scholar 

  50. Inbal A, Englender T, Kornbrot N, et al. Identification of 3 candidate mutations causing type IIA von Willebrand disease using a rapid, non radioactive, allele-specific hybridization method. Blood 1993;82:830–36.

    PubMed  CAS  Google Scholar 

  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 Wille-brand disease. Blood 1991;78(suppl.1):67a(Abstract).

    Google Scholar 

  52. Donner M, Kristoffersson AC, Lenk H, et al. Type IIB von Willebrand’s disease: Gene mutations and clinical presentation in nine families from Denmark, Germany and Sweden. Br J Haemat 1992;82:58–65.

    Article  CAS  Google Scholar 

  53. 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 Ib but not to collagen or heparin. J Biol Chem 1992;267: 21187–92.

    PubMed  CAS  Google Scholar 

  54. Gaucher C, Parquet-Gernez A, Hanss M, Horellou MH, Goudemand M, Mazurier C. Potential new mutations in French Families with type IIA and IIB von Willebrand’s disease. Proc XX International Congress, World Federation of Hemophilia, Athens, 1992:176 (Abstract).

    Google Scholar 

Download references

Authors
  1. C. Mazurier
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Red Cross Blood Bank Groningen-Drenthe, The Netherlands

    C. Th. Smit Sibinga  & P. C. Das  & 

  2. Leiden, The Netherlands

    E. Briët

Rights and permissions

Reprints and permissions

Copyright information

© 1995 Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

Mazurier, C. (1995). Molecular Biology of the Various Types of von Willebrand Disease. In: Sibinga, C.T.S., Das, P.C., Briët, E. (eds) Hereditary Diseases and Blood Transfusion. Developments in Hematology and Immunology, vol 30. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-2017-7_2

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-2017-7_2

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-5834-3

  • Online ISBN: 978-1-4615-2017-7

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation