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The inheritance of type I and type III von Willebrand's disease in Israel: linkage analysis, carrier detection and prenatal diagnosis using three intragenic restriction fragment length polymorphisms

Three intragenic restriction fragment length polymorphisms (RFLPs) were used to study linkage and analyse the mode of inheritance in type I and type III von Willebrand's disease (VWD). In two families linkage was established between Sac I RFLPs and the inheritance of type I vWD. RFLP analysis of amniocyte DNA from a potentially affected foetus enabled us to establish a prenatal diagnosis of vWD in a third family with type I vWD. Linkage was also established in four families between the Sac I and two Taq I RFLPs and the inheritance of type III vWD. AH type III probands were homozygotes and inherited the same mutant vWF allele from both parents. HeteToiygous carriers from one type III family were phenotypically normal and could be detected only by linkage analysis, whereas carriers from the remaining three type III families were asymptomatic but had decreased values of vWF antigen and activity. RFLP-based linkage analysis of vWD alleles provides a way to improve the diagnostic precision, detect carriers, and may be useful for prenatal diagnosis of type III vWD.