2A型血管性血友病vWF基因Ala737→Glu的突变  

Mutation (Ala737→Glu) in type 2A von Willebrand disease

作　　者：王迎春[1] 张敬宇[1] 万海英[1] 施纪文 李震宇[1] 阮长耿[1] 

机构地区：[1]苏州医学院附属第一医院,江苏省血液研究所血栓与止血研究室

出　　处：《中华血液学杂志》1999年第3期117-119,共3页Chinese Journal of Hematology

基　　金：国家自然科学基金

摘　　要：目的阐明２Ａ型血管性血友病（ｖＷＤ）临床表现型与基因型的相关性。方法研究来自同一家系的２例患者，他们具有初期止血障碍的出血特点，ｖＷＦ∶Ａｇ和ＦⅧ∶ＣＡｇ减少，瑞斯托霉素诱导的血小板聚集明显降低，大、中多聚物分子消失，临床表型符合２Ａ型血管性血友病。用聚合酶链反应方法扩增患者的ｖＷＦ基因的２８号外显子，并用特异性内切酶的方法获得真基因，变性梯度凝胶电泳（ＤＧＧＥ）筛选突变基因，对电泳行为异常的片段进行测序。结果该２Ａ型ｖＷＤ家系ｖＷＦ基因的４３７０～４５９０区域ＤＧＧＥ有明显减慢的条带。ＤＮＡ序列测定，表明在ｖＷＦ基因４４９９位Ｃ→Ａ致ｖＷＦ蛋白Ａ２区域Ａｌａ７３７→Ｇｌｕ。结论该突变有助于研究ｖＷＦ蛋白功能域的精细功能及ｖＷＤ表型与基因型的相关性。Objective To identify mechanism of molecular pathogenesis and relationship between phenotype and genotype of von Willebrand disease (vWD). Methods Two patients from a family were studied. They were diagnosed as type 2A vWD showing prolonged bleeding time, markedly decreased vWF∶Ag and FⅧ∶C Ag and absence of high and intermediate molecular weight form of von Willebrand factor multimers in plasma. The 28th exon of authenticity vWF gene was obtained by polymerase chain reaction and PAGE and then screened by denaturing gradient electrophoresis (DGGE). The abnormal bands were sequenced. Results A heterozygous C→A transition was identified, resulting in an ala737glu mutation in the A2 domain of the mature vWF subunit. Conclusion The new mutation will be a tool for the study of the structure and function of vWF.

关 键 词：血友病 血管性血友病 VWF基因 点突变 PCR 

分 类 号：R554.104[医药卫生—血液循环系统疾病]