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Molecular Genetics of von Willebrand Disease

  1. Derrick John Bowen

Published Online: 15 DEC 2008

DOI: 10.1002/9780470015902.a0021447

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How to Cite

John Bowen, D. 2008. Molecular Genetics of von Willebrand Disease. eLS. .

Author Information

  1. Cardiff University, School of Medicine, Cardiff, UK

Publication History

  1. Published Online: 15 DEC 2008

Abstract

In 1926, Dr Erik von Willebrand first described the autosomal bleeding disorder that we now call von Willebrand disease (VWD). Since then, the protein responsible – eponomously named von Willebrand factor (VWF) – has been identified, the gene encoding the protein has been localized , the gene sequence has been determined and many mutations within the gene that lead to a deficiency or dysfunction of VWF and cause VWD have been characterized. Through the concerted efforts of scientists and clinicians, there is now considerable understanding of the molecular genetics of VWD and, through studies done both in vitro and in vivo, the mechanism of disease has been revealed for many of the characterized gene defects. Despite the complexities of both the VWF protein and its gene, we have a detailed picture of the molecular genetics of VWD. This review aims to provide an informative summary of current knowledge.

Key concepts

  • von Willebrand factor (VWF) is a polymeric (multimeric) blood protein that is essential for the initial stages of blood clot formation.

  • VWF has several biological activities that are important for its role in haemostasis, including binding to platelet glycoprotein Ib, coagulation factor VIII, collagen.

  • VWF has a complex biochemistry that is influenced by independent modifiers such as ABO blood group and the metalloprotease ADAMTS13.

  • von Willebrand disease (VWD) is classified into three types according to the quantity and functional activity of VWF: type 1, type 2 and type 3. Type 2 VWD is further subdivided according the functional defect present: type 2A, 2B, 2M and 2N.

  • The genetic basis for VWD is highly heterogeneous; the disease shows dominant inheritance for some mutations and recessive inheritance for others.

  • Mutations that cause milder forms of the disease show variable penetrance and this, in part relates to other modifying factors such as ABO blood group and possibly ADAMTS13.

  • The relationship between cause and effect is understood for some mutations but not for all.

Keywords:

  • von Willebrand factor;
  • von Willebrand disease;
  • primary haemostasis;
  • ADAMTS13;
  • platelets;
  • Bleeding