Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

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Von Willebrand Disease (VWS) [D.68.0]

OMIM numbers: 193400 (type 1), 613554 (type 2), 277480 (type 3), 613160 (VWF)

Dr. rer. nat. Christoph Marschall

Scientific Background

VWS is a congenital or acquired disorder of the coagulation system and is caused by quantitative or qualitative changes in the von Willebrand factor (VWF) or factor 8. The most important functions of the VWF include promotion of platelet adhesion through glycoprotein Ib, which is localized on the surface of thrombocytes, as well as binding of factor VIII which protects the factor of rapid degradation. Thrombocytic adhesion depends on the large multimers of VWF.

All functions of VWF are affected by mutations in the VWF gene that have a general, quantitative effect on the expression of VWF. Mutations which impair the formation of large multimers only influence the VWF function in primary hemostasis. If, however, the FVIII binding region is damaged, the function in secondary hemostasis is affected. The quantitative effects are categorized into partial quantitative deficiency (type I) and complete deficiency (type III). Qualitative defects (type II) are very heterogeneous. By the identification of specific mutations which cause reduced expression of VWF, disorders of the posttranslational modification, impairment of the intracellular transport or functional defects, the highly heterogenous clinical phenotype can be associated with the genotype. Mutational analysis can aid in classification, establishing a correct diagnosis and in choosing the appropriate treatment.