RECESSIVE INHERITANCE OF VONWILLEBRANDS DISEASE TYPE-I

The inheritance of type I von Willebrand's disease is thought to be au tosomally dominant. The laboratory profile may, however, vary between affected people, even within a single family. There is also a large va riation in the severity of clinical symptoms. To see if there is an as sociation between the von Willebrand factor genotype, the laboratory p rofile, and the severity of the clinical symptoms we did a genetic ana lysis of four families with type I von Willebrand's disease. The proba nd 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 identifie d mutations, which was shared by the probands of three of the four fam ilies, may have a carrier prevalence of 1:50 in the general population . These results suggest that the inheritance of von Willebrand's disea se is often recessive rather than dominant and so have important impli cations for diagnosis and genetic counselling.