Carrier detection in severe von Willebrand’s disease

Abstract

Von Willebrand’s disease (vWD) is an inherited bleeding disorder, caused by a defect of von Willebrand’s factor (vWF), a multimeric high molecular weight glycoprotein. It is sub-characterised into types 1, 2 and 3 vWD depending on quantitative or qualitative defect of vWF. Prenatal diagnosis and carrier detection are often sought by families affected by type 3 vWD. Five diagnosed index patients with severe type 3 vWD and their family members were the subjects of this study. Two markers (vWF 1 and vWF 2) were used in the polymorphic region of ATCT repeats (variable number of tandem repeat, VNTR) within intron 40 of the vWF gene. The study was done to determine the allelic frequency of these markers in normal Indians and to identify the carriers in type 3 vWD in India. In the five families studied by both markers (vWF 1 and vWF 2), Mendelian inheritance of the VNTR bands were demonstrated, and in all cases the band seen in offspring was present in the parents. Heterozygosity is seen in 78% of normal controls for vWF 1 marker and 80% for vWF 2 marker. Since the heterozygosity frequency of these two markers is high, 70% of carriers of vWD could be successfully detected by this method. It is thus concluded that VNTR gene tracking may be a useful approach for carrier detection in the type 3 vWD in developing countries.