An infrequent DNA polymorphism associated with severe von Willebrand's disease

Genomic DNA of six unrelated Dutch patients with severe von Willebrand's disease (vWD) was submitted to restriction fragment length polymorphism analysis. We observed a strong association between a 36 kb allele detected by a partial complementary DNA probe (pvWF 1100) and the restriction enzyme XbaI with severe von Willebrand's disease. This 36 kb allele is rare (allele frequency of 7%) both in the general population and in patients with autosomal dominant types of von Willebrand's disease. Three of our six patients were found to be homozygous for this allele while two others were heterozygous. The association of this rare XbaI allele with severe vWD enables carrier detection and prenatal diagnosis in these families. The high frequency (67%) of the 36 kb allele observed in this patient group raises the possibility that a subgroup of patients with severe vWD has a genetic defect with a common origin.