HEMOPHILIA-A OR VON-WILLEBRAND DISEASE

Seven members of the same family were studied on several occasions due to a history of hemorrhages. The propositus, a 12-year-old boy, his s ister, one brother, and their father all had a low plasma factor VIII (FVIII) level. Von Willebrand factor (VWF) activity, vWF multimeric an alysis, and vWF factor domain for binding to FVIII were normal in all seven subjects. The sister had a normal 46XX karyotype. The study of t wo intragenic restriction fragment length polymorphisms (RFLPs) and tw o closely linked, highly polymorphic extragenic markers showed a pheno typic expression of mild hemophilia A, which suggests that the sister of the propositus is homozygous or compound heterozygous at the hemoph ilia A locus. She would have inherited two hemophilic genes: one from her carrier mother and the other from her father, a mild hemophiliac.