title: A first Taiwanese Chinese family of type 2B von Willebrand disease with R1306W mutation.
abstract: Clinical, laboratory and genetic defect of a Taiwanese family with type 2B von Willebrand disease (VWD) were studied. The proband was a 55-year-old woman who gave birth to two daughters and one son aged 30, 29 and 27, respectively. All had abnormal mucocutaneous bleedings since their childhood. In proband, PT, PTT and platelet count were normal; template bleeding time was 14 min; VIII:C was 51%, von Willebrand factor antigen (VWF:Ag), 42% and von Willerand factor ristocetin-cofactor (VWF:RCo, 15%); ristocetin-induced platelet aggregation (RIPA) at 0.3 and 0.6 mg/ml of ristocetin was 16% and 68%, respectively. The enhanced response to ristocetin was identified to be in plasma, not in platelet itself, by mixing studies. Analysis of von Willebrand factor (VWF) multimer of plasma but not of platelets showed absence of high-molecular weight (HMW) multimer. All three children had similar laboratory findings. Exon 28 of VWF gene was amplified using polymerase chain reaction (PCR) and sequenced. The proband and three children were all found to be heterozygous for C to T transition at nucleotide 3916 resulting in Arg 1306 Trp (R1306W) substitution. This mutation in the glycoprotein Ib (GPIb)-binding site has been found to increase the affinity of plasma VWF for platelets, and thus cause loss of HMW multimers and often thrombocytopenia. In conclusion, a first report of type 2B VWD in a Taiwanese Chinese family who show R1306W mutation in VWF gene was described.
authors.affiliation: Department of Laboratory Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan. smc@ha.mc.ntu.edu.tw
authors.forename: Ming-Ching
authors.initials: MC
authors.lastname: Shen
authors.forename: Jen-Shiou
authors.initials: JS
authors.lastname: Lin
authors.forename: David Shih-Yao
authors.initials: DS
authors.lastname: Lin
authors.forename: Su-Chuen
authors.initials: SC
authors.lastname: Hsu
authors.forename: Bodo
authors.initials: B
authors.lastname: Lin
mesh_terms: D000328:Adult; D001665:Binding Sites / Q000235:genetics; D001780:Blood Coagulation Tests; D001792:Blood Platelets / Q000378:metabolism*; D004252:DNA Mutational Analysis; D019281:Dimerization; D005091:Exons; D005192:Family Health; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010979:Platelet Function Tests; D017354:Point Mutation; D013624:Taiwan; D013921:Thrombocytopenia / Q000209:etiology; D014842:von Willebrand Diseases / Q000235:genetics*; D014841:von Willebrand Factor / Q000235:genetics / Q000378:metabolism
chemical_list: D014841:von Willebrand Factor