Phenotype and genotype analysis of two Chinese pedigrees with type 3 von Willebrand diseases / 中华医学遗传学杂志

ABSTRACT

<p><b>OBJECTIVE</b>To analyze the phenotype and genotype of two Chinese pedigrees with von Willebrand diseases, and to investigate the molecular pathogenesis.</p><p><b>METHODS</b>Bleeding time (BT), activated partial thromboplastin time (APTT), ristocetin-induced platelet aggregation (RIPA), von Willebrand factor-ristocetin cofactor (vWFRco), von Willebrand factor antigen (vWFAg), von Willebrand factor activity (vWFA), von Willebrand factor collagen binding assay (vWFCB) and multimer analysis were used for phenotype diagnosis. DNA was extracted. All of the 52 exons and exon-intron bounda ries of the VWF gene were amplified with polymerase chain reaction(PCR) and analyzed by direct sequencing.</p><p><b>RESULTS</b>APTT and BT were prolonged. Plasma RIPA, vWFRco, vWFAg, vWFA and vWFCB was significantly decreased. No VWF multimer can be found by plasma VWF multimer analysis. Homozygous insertional mutation g.82888_82889insCATG in exon 17 was found in proband A. Compound heterozygous mutations g.94865 G to A (Trp856stop) in exon 20 and g.110698_110699delinsG in exon 28 were found in proband B.</p><p><b>CONCLUSION</b>Homozygous insertional mutation g.82888_82889insCATG and compound heterozygous mutations g.94865G to A(Trp856X) and g.110698_110699delinsG probably have respectively induced type 3 von Willebrand diseases in the two probands.</p>