Study On The Clinical Phenotype And Mechanism In Two Chinese Pedigrees With Von Willebrand Disease

Objective: The aim of this study was to investigate the clinical phenotype andthe mutations of vWF exon28,GP1BA and ADAMTS13genes in two Chinesepedigrees with von Willebrand disease(VWD)，and to explore the mechanism ofVWD.Methods: Five cases with VWD from two unrelated families were enrolled inthis study. Total DNA of all cases were extracted from peripheral blood. Allexons of GP1BA、ADAMTS13genes, as well as the exon28of vWF genewere amplified by PCR and directly sequenced. The DNA sequence files werecompared to wild type sequence using Chromas software.Results: One pedigree showed a novel mutation, G1206A of GP1BA gene,which resulted in a Glu429Lys amino acid substitution. And showed aVNTR B/C heterozygote in GP1BA gene, and a male patient and his fathershowed a deletion of39bases rather than a VNTR. In addition, severalpolymorphisms including G4039A, A4391G, G4664C, and T4891C in exon28of vWF gene were identified. There was no genetic variant found in theADAMTS13gene.Conclusion: The G1206A mutation and the deletion of39bases of GP1BA gene may be the causes of PT-VWD. Furthermore, the polymorphisms ofG4039A, A4391G, G4664C, and T4891C in exon28of vWF gene maycontribute to the pathogenesis of2B VWD.