一例遗传性凝血因子Ⅴ缺乏症发病机制研究  

Studies on hereditary deficiency of coagulation factor Ⅴ

作　　者：谢飞[1] 程烽[1] 朱晓辉[1] 宋昌礼[1] 兰风华[1] 朱忠勇[1] 

机构地区：[1]南京军区福州总医院全军医学检验中心实验科,350025

出　　处：《中华血液学杂志》2001年第9期453-456,共4页Chinese Journal of Hematology

摘　　要：目的　研究遗传性凝血因子Ⅴ (FⅤ )缺乏症的发病机制。方法　通过免疫学方法和发色底物法检测血浆和血小板中的FⅤ含量 ,采用PCR产物直接测序和限制性酶切分析FⅤ基因 ,应用分子模建对所鉴定突变的生物结构病理学进行研究。结果　先证者血浆和血小板中FⅤ均缺乏。先证者FⅤ基因第 176 3位核苷酸存在A→C突变 (176 3A→C ,EMBLAJ2 972 5 4)。模建分析表明 ,该突变将导致分子内部形成空洞 ,并可能破坏Tyr5 30与Glu330之间形成的氢键。结论　 176 3A→C突变将导致FⅤ稳定性降低 。Objective To explore the mechanisms of hereditary deficiency of coagulation factor Ⅴ (FⅤ). Methods The amount of FⅤ in plasma and platelets was assayed by immunological and biochemical method, FⅤ gene analysis by PCR product sequencing and restriction enzyme analysing, and the biostructural pathology of the identified mutation by molecular modeling. Results No detectable FⅤ fragments and FⅤ activity were found in the plasma and platelets from the proband of the affected family.His gene analysis revealed a 1?763A→C substitution in a FⅤ allele gene. The mutation might cause the loss of the hydrogen bond between conservative Tyr530 and Glu330, and form a cavity in the protein core. Conclusion The 1?763A→C mutation might cause the instability of FⅤ and be the important mechanism for the hereditary deficiency of FⅤ.

关 键 词：凝血因子V 基因突变 分子模拟 遗传性凝血因子V缺乏症 发病机制 

分 类 号：R596[医药卫生—内科学]