Molecular genetics of von Willebrand disease

Abstract

Due to the multifunctional character of von Willebrand factor (VWF), its complex biosynthesis and structure, many different disease causing molecular mechanisms exist which explain the well known marked heterogeneity of clinical symptoms in von Willebrand disease (VWD). Identification of specific mutations that can either cause complete or partial absence of VWF, interfere with post-translation processing of VWF like dimerisation and multimerisation, impair intracellular transport or disturb particular functions of VWF, offered the opportunity for structure/function studies of VWF and genotype/phenotype analysis of VWD. Today the molecular tools for such studies are readily available, enabling us to identify the molecular defects in a reasonable time even in the case of the large and complex VWF gene with its 52 exons. Mutation analysis can help to find the correct diagnosis and to classify patients with VWD which may be crucial to choose the adequate therapy. It can also identify unaffected carriers of the disease gene among family members of patients with VWD. Furthermore, mutation analysis and the conclusions drawn from such data can further help to understand the molecular mechanisms of VWF not only in bleeding but also in arterial thrombotic disease.