Arg304Trp导致的遗传性凝血因子Ⅶ缺陷症家系分析

目的对1例姨表近亲结婚的遗传性凝血因子Ⅶ（coagulation factorⅦ,FⅦ）缺陷症家系进行表型与基因型分析。方法检测血浆中凝血酶原时间（prothrombin time,PT）、FⅦ促凝活性（FⅦprocoagulant activity,FⅦ：C）及其它凝血指标以明确诊断;用DNA直接测序法对先证者及家庭成员FⅦ基因的全部外显子及其侧翼、启动子区进行分析,寻找基因突变,用反向测序证实所发现的突变。结果先证者的PT和FⅦ：C明显异常,分别为35.1s和3%;其父亲、母亲、大儿子和小儿子的PT稍延长,FⅦ：C明显降低。先证者FⅦ基因外显子8存在11348C→T纯合突变导致Arg304Trp;其父亲为该突变位点的杂合子,其母亲、大儿子和小儿子均为Arg304Trp杂合突变和Arg353Gln杂合多态性。结论先证者纯合突变Arg304Trp遗传自近亲结婚且具有相同杂合突变位点的父母。Arg353Gln多态性可能不是影响该家系成员血浆FⅦ：C水平的主要因素。     

纯合子His348G1n导致的遗传性凝血因子Ⅶ缺乏症家系分析

目的 对1个姨表近亲结婚的遗传性凝血因子Ⅷ(coagulation factorⅦ,FⅦ)缺乏症家系进行基因突变检测,探讨其分子发病机制.方法 检测凝血酶原时间(prothrombin time,PT)、活化部分凝血活酶时间、纤维蛋白原、血浆凝血因子活性等指标以明确诊断;用DNA直接测序法对先证者及家系成员FⅦ基因的全部外显子及侧翼、5'和3'非翻译区进行分析,寻找基因突变,用反向测序证实所发生的突变.结果 先证者PT(30.9 s)和FⅦ活性(3%)明显异常,女儿、父亲和母亲的PT(分别为21.2 s、16.3 s和16.1 s)稍延长和FⅦ活性(分别为22%、25%和35%)减低,胞弟各指标均在正常范围内;先证者FⅦ基因第8外显子的11482位为纯合T→G导致氨基酸His348Gln;女儿、父亲和母亲为His348Gln杂合子,胞弟为正常野生型.结论 该遗传性FⅦ缺乏症家系为纯合子错义突变His348Gln,推测此突变遗传自近亲结婚具有该杂合子的父母.

Abstract：

Obiective To investigate the gene mutation and the molecular pathogenesis of an inherited coagulation factor Ⅶ (F Ⅶ ) deficiency pedigree with consanguineous marriage. Methods The diagnosis was validated by coagulant parameter assay on the prothrombin time (PT), activated partial thromboplastin time, fibrinogen and coagulation factor activity. F Ⅶ gene mutations were analyzed in the proband and other family members by direct DNA sequencing of the PCR products of all exons, exon-intron boundaries and 5' and 3' untranslated sequences. The mutations were confirmed by reverse sequencing.Results The values of PT and FⅦ activity in the proband were significantly abnormal, they were 30. 9 s and 3% respectively. The PT of her daughter, father and mother was slightly extended to 21.2 s, 16.3 s and 16. 1 s respectively, and the FⅦ activity was reduced to 22%, 25% and 35% respectively. The coagulant parameters of her younger brother were within normal range. Homozygous T→G transition at position 11482 in exon 8 was identified in the proband resulting in His348Gln, and heterozygosity for His348Gln was confirmed in her daughter and her parents, and the normal wild-type was observed in her younger brother. Conclusion Homozygous missense mutation of His348Gln was found in a pedigree of hereditary FⅦ deficiency. The mutation was inherited from her heterozygote parents.     

丹红与丹参川芎嗪注射液对急性冠状动脉综合征所致凝血因子Ⅶ异常的调节作用比较

目的 比较丹红注射液与丹参川芎嗪注射液对急性冠状动脉综合征(acute coronary syndrome,ACS)导致的凝血因子Ⅶ水平异常的调节作用.方法 将全部患者完全随机分为3组各60例,对照组采用西医常规治疗,丹红注射液组(A组)、丹参川芎嗪注射液组(B组)在对照组治疗基础上,分别给予丹红注射液和丹参川芎嗪注射液治疗,观察两药对ACS所致凝血因子Ⅶ水平异常的调节作用.结果 B组对凝血因子Ⅶ水平异常的调节作用优于A组(χ~2=3.67,P＜0.05),A、B两组对凝血因子Ⅶ的疗效均优于对照组(P＜0.05).结论 丹参川芎嗪注射液对凝血因子Ⅶ水平的调节作用优于丹红注射液;丹红注射液和丹参川芎嗪注射液对凝血因子Ⅶ水平有调节作用.