一个遗传性凝血因子Ⅴ缺陷症家系表型与基因分析  

Phenotype and gene analysis of a family with hereditary coagulation factor V deficiency

作　　者：杜长宝[1] 杨婷[1] 祝进[1] 杨丽红[2] 程晓丽[2] 王明山[2] DU Chang -bao;YANG Ting;ZHU Jin;YANG Li -hong;CHENG Xiao -li;WANG Ming -shan(Clinical Laboratory,Quzhou People's Hospital,Quzhou,Zhejiang 324000,China)

机构地区：[1]衢州市人民医院检验科,浙江衢州324000 [2]温州医科大学.附属第一医院检验科,浙江温州325000

出　　处：《中国卫生检验杂志》2018年第23期2863-2866,共4页Chinese Journal of Health Laboratory Technology

基　　金：温州市科技局项目(2015Y0123)

摘　　要：目的对1个由近亲结婚引起的遗传性凝血因子Ⅴ(FⅤ)缺陷症家系进行表型与基因分析,探讨其分子发病机制。方法检测先证者及家系成员(三代6名成员)凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、纤维蛋白原(FIB)、血浆FⅤ活性(FⅤ∶C)和血浆FⅤ抗原(FⅤ∶Ag)等指标进行表型诊断,用DNA直接测序法分析先证者F5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,发现突变位点用反向测序予以证实,并用医学生物软件对该突变进行分析。结果先证者PT和APTT均明显延长,分别为20. 5 s和51. 7 s,其FⅤ∶C和FⅤ∶Ag分别为11. 0%和12. 0%。先证者F5基因第5号外显子上发现c. 653T> C纯合突变,导致Phe190Ser,其父亲、母亲、女儿为Phe190Ser杂合子,FⅤ∶C和FⅤ∶Ag也均有不同程度下降(分别为54%、47%、60%和61. 4%、52. 1%、56. 5%),丈夫和姐姐为正常野生型,其FⅤ∶C和FⅤ∶Ag均在正常水平。生物软件分析均显示该突变对FⅤ蛋白产生危害。结论 F5基因第5号外显子上c. 653T> C的纯合突变是导致先证者携带Phe190Ser原因,且该Phe190Ser突变与先证者FⅤ水平减低有关。Objective The phenotypic and genetic analysis of a family with hereditary coagulation factor V( FV) deficiency caused by consanguineous marriage was carried out to explore its molecular pathogenesis. Methods The prothrombin time( PT),activated partial thromboplastin time( APTT),fibrinogen( FIB),plasma FV activity( FV∶C) and plasma FV antigen( FV∶Ag) of the proband and her family members( 6 members of 3 generations) were measured to analyze the phenotype. All the exons,5’ and 3’ untranslated regions of the F5 gene of the proband and the corresponding mutant site regions of the proband’s family members were analyzed by direct DNA sequencing. When the mutant sites were found,they were confirmed by reverse sequencing and analyzed by medical bioinformatics software. Results The PT and APTT of the proband were prolonged to 20. 5 s and 51. 7 s. The FV∶C and FV∶Ag decreased to 11. 0% and 12. 0%. A homozygous mutation of c. 653 T > C was found in the 5 thexon of the F5 gene of the proband,causing Phe190 Ser. The father,mother and daughters of the proband were Phe190 Ser heterozygotes and their FV∶C and FV∶Ag( 54%,47%,60%,61. 4%,52. 1%,56. 5%,respectively) also decreased in different degrees. The husband and sister of the proband were normal wild types and their FV∶C and FV∶Ag were normal. Bioinformatics software analysis showed that the mutation was harmful to FV protein. Conclusion The homozygous mutation of c. 653 T > C in exon 5 of the F5 gene was the cause of probands carrying Phe190 Ser,and the Phe190 Ser mutation was associated with reduced proband FV levels.

关 键 词：近亲婚配 凝血因子V缺陷症 基因突变 生物信息学 

分 类 号：R554[医药卫生—血液循环系统疾病]