von Willebrand disease with G4022A mutation (vWd Sungnam): A case report

A 10-year-old male patient affected by type 2 von Willebrand disease (VWD) and his family members were investigated by hemostatic and molecular geneti c studies. The propositus, who experienced frequent bleeding episodes, was characterized by a normal level of von Willebrand factor (VWF) antigen (54% ), reduced vWF ristocetin cofactor activity (5%), decreased factor VIII clo tting activity (25%) and absent high molecular weight multimers in the plas ma. An exon 28 fragment coding for the A1 and A2 domains was amplified by p olymerase chain reaction and sequenced, We found a heterozygous mutation (G 4022A), producing an additional Pstl restriction site, which resulted in th e substitution of Arg578Gln, Family studies, including the parents and a br other, were negative for this mutation and vWF abnormalities were not obser ved. We confirmed that G to A mutation in the region of the platelet glycop rotein Ib binding domain of VWF causes the qualitative type 2 defect in von Willebrand disease.