Recessive inheritance of von Willebrand's disease type I

Abstract

The inheritance of type I von Willebrand's disease is thought to be autosomally dominant. The laboratory profile may, however, vary between affected people, even within a single family. There is also a large variation in the severity of clinical symptoms. To see if there is an association between the von Willebrand factor genotype, the laboratory profile, and the severity of the clinical symptoms we did a genetic analysis of four families with type I von Willebrand's disease. The proband of each family proved to be a compound heterozygote for defects in the von Willebrand factor gene. Simple heterozygotes in these families were either symptomless or only mildly affected. One of the identified mutations, which was shared by the probands of three of the four families, may have a carrier prevalence of 1:50 in the general population. These results suggest that the inheritance of von Willebrand's disease is often recessive rather than dominant and so have important implications for diagnosis and genetic counselling.