[Molecular study of type 2 von Willebrand disease]

von Willebrand disease is an inherited bleeding disorders caused by mutations in the von Willebrand factor gene. We attempted to characterise the phenotype and the genotype in the first five families in Czech Republic affected by this heterogeneous disorder.

The level of FVIII was measured by the one stage assay, the vWF:Ag by the immunoelectrophoresis, vWF:RiCo by aggregometry. For the vWF multimer analysis a western blot based technique was used. The vWF binding to FVIII was evaluated by the ELISA method. Two families were classified as the type 2A, one as the type 2B and two as the combined type 1/2N. Based on that knowledge, parts of the vWF gene were selected for genetic analysis. The previously described mutations Arg1374His and Gly1579Arg were identified in two families with the type 2A. In the family with type 2B a substitution Arg1308Cys was detected. In one family with the type 1/2N, two different previously described defects were found on the separate alleles of the vWF gene: a deletion of cytosine 2435 and a polymorphism Arg854Gln. Compound heterzygotes had the type 1/2N phenotype, while a carriers of the deletion had type 1 phenotype. In the second type 1/2N family, only the amino acid substitutions Thr791Me was found explaining the qualitative defect. A mutation underlying the quantitative deficiency needs to be searched for throughout the entire vWF gene.

Based on the characterisation of the phenotype and genotype, five apparently unrelated families with the von Willebrand disease were diagnosed according to the revised classification. Our work represents laboratory basis for further studies into von Willebrand disease in Czech Republic.