His348Gln杂合突变伴Arg353Gln杂合多态性导致的遗传性凝血因子Ⅶ缺陷症家系分析  

Study of an inherited coagulation factor VII deficiency pedigree caused by heterozygous mutation of His348Gln combined with heterozygous polymorphism of Arg353Gln

作　　者：杨小丽[1] 金艳慧[1] 王莹宇 王明山[1] 

机构地区：[1]温州医科大学附属第一医院医学检验中心,浙江温州325000

出　　处：《温州医学院学报》2013年第12期788-791,共4页Journal of Wenzhou Medical College

基　　金：温州市科技局科研基金资助项目(Y20100284;Y20110074)

摘　　要：目的 :对1例遗传性凝血因子Ⅶ(FⅦ)缺陷患者进行基因分析和家系调查,初步探讨其发病的分子机制。方法:检测先证者及其家系成员凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、纤维蛋白原(FIB)、凝血酶原活性(FII:C)、凝血因子V活性(FV:C)、FVII活性(FVII:C)和凝血因子X活性(FX:C)及FVII抗原(FVII:Ag)等进行表型诊断;用DNA直接测序法分析先证者F7基因的全部外显子、侧翼、5’和3’非翻译区及家系成员相应的突变位点区域,用反向测序证实所发生的突变。结果:先证者PT延长为22.4 s,FVII:C和FVII:Ag明显降低,分别为7%和10%;父亲、母亲、姐姐及儿子的PT正常或稍延长,FVII:C分别为63%、54%、57%和46%,FVII:Ag分别为67%、53%、61%和49%;先证者和所有家系成员的APTT及其他凝血指标均在正常参考范围内。测序发现先证者F7基因第8号外显子存在g.11482T>G(His348Gln)杂合突变和g.11496 G>A(Arg353Gln)杂合多态性;其母亲、姐姐、儿子均存在F7基因g.11482T>G杂合突变;父亲存在F7基因g.11496 G>A杂合多态性。结论:F7基因His348Gln杂合突变协同Arg353Gln杂合多态性是导致该先证者FⅦ缺陷症的分子机制。Objective： To identify the gene mutation and explore the molecular pathogenesis of an inherited factor VII deficiency pedigree. Methods： Prothrombin time （PT）, activated partial thromboplastin time （APTT）, fibrinogen （Fg）, F II activity （F II：C）, FV activity （FV：C）, F VII activity （F VII：C）, FX activity （FX：C） and F VII antigen （F VII：Ag） were measured for phenotype diagnosis. All the exons, exon-intron boundaries and 5＇, 3＇untranslated sequences of F7 gene of the proband and other family members were analyzed by direct sequencing. The detected mutations were confirmed by sequencing the complementary strand. Results： The value of PT in the proband was extended to 22.4 s. and the F VII：C and F VII： Ag of the proband were obviously reduced, which were 7% and 10% respectively. The PT of his father, mother, sister and son were either slightly prolonged or normal, their FVII：C （63%, 54%, 57% and 46%, respectively） and FVII：Ag （67%, 53%, 61% and 49%, respectively） were reduced. The APTY and other coagulant parameters of the proband and other family members were within normal range. Genetic analysis revealed T to G transition at 11482 and G to A transition at 11496 in the exon 8 of F7 gene of the proband （which resulted in His348Gln missense mutation and Arg353Gln polymorphism, respectively）, both of them were heterozygous. The heterozygous polymorphism （Arg353Gln） was identified in his father, while the same heterozygous mutation （His348Gln） was identified in other family members. Conclusion： The heterozygous mutation of His348Gln combined with heterozygous polymorphism of Arg353Gln in F7 gene detected from the proband relates to the F VII deficiency.

关 键 词：凝血因子Ⅶ缺陷 遗传性 突变 多态性 基因分析 

分 类 号：R554.9[医药卫生—血液循环系统疾病]