Molecular Study of the Type 2 von Willebrand Disease

Overview

Background.
von Willebrand disease is an inherited bleeding disorders caused by mutations in the von Willebrandfactor gene.We attempted to characterise the phenotype and the genotype in the first five families in Czech Republicaffected by this heterogeneous disorder.Methods and Results. 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 techniqe was used.The vWF binding to FVIII was evaluated by the ELISA method. Two families were classified as the type 2A, oneas the type 2B and two as the combined type 1/2N. Based on that knowledge, parts of the vWF gene were selectedfor genetic analysis. The previously describedmutations Arg1374His andGly1579Argwere identified in two familieswith the type 2A. In the family with type 2B a substitution Arg1308Cys was detected. In one family with the type1/2N, two different previously described defects were found on the separate alleles of the vWF gene: a deletion ofcytosine 2435 and a polymorphism Arg854Gln. Compound heterzygotes had the type 1/2N phenotype, whilea carriers of the deletion had type 1 phenotype. In the second type 1/2N family, only the amino acid substitutionsThr791Me was found explaining the qualitative defect. A mutation underlying the quantitative deficiency needs tobe searched for throughout the entire vWF gene.Conclusions. Based on the characterisation of the phenotype and genotype, five apparently unrelated familes withthe von Willebrand disease were diagnosed according to the revised classification. Our work represents laboratorybasis for furhter studies into von Willebrand disease in Czech Republic.

Key words:
von Willebrand factor, von Willebrand disease, vWF gene.