15例遗传性凝血因子V缺陷症先证者的临床特征与基因突变分析  

Clinical features and gene mutation analysis of fifteen probands with hereditary coagulation factor V deficiency

作　　者：林双女 叶银才 陈碧乐[1] 谢作听[1] 王明山[2] LIN Shuangnv;YE Yincai;CHEN Bile;XIE Zuoting;WANG Mingshan(Department of Blood Transfusion,the First Affiliated Hospital of Wenzhou Medical University,Wenzhou 325015,Zhejiang,China;Center of Laboratory Medicine,the First Affiliated Hospital of Wenzhou Medical University,Wenzhou 325015,Zhejiang,China)

机构地区：[1]温州医科大学附属第一医院输血科,浙江温州325015 [2]温州医科大学附属第一医院医学检验中心,浙江温州325015

出　　处：《临床检验杂志》2024年第6期425-429,共5页Chinese Journal of Clinical Laboratory Science

基　　金：温州市科学技术局(Y2023508)。

摘　　要：目的分析15个遗传性凝血因子V(FV)缺陷症先证者的临床特征与基因突变类型,初步探讨其可能的分子致病机制。方法采用一期凝固法和ELISA法分别检测FV活性(FV:C)和FV抗原(FV:Ag)。用PCR扩增患者F5基因的25个外显子及其侧翼序列,并直接测序。利用蛋白质模型分析其可能的分子机制。结果在5例FV:C大于10%的先证者中,仅有1例出现轻微出血症状;在10例FV:C小于10%的先证者中,7例表现出各种出血症状。15例先证者共检出12个基因突变位点(其中8个为新的突变,1个为致病的多态性)。蛋白质模型分析表明,所有6种错义突变都会导致FV蛋白的构象改变,其中2种(p.Ser1781Arg和p.Asp96His)会减少氢键数量,从而导致局部蛋白质结构不稳定。结论这些遗传性FV缺陷症先证者的FV水平与各自的F5基因突变有关,其FV水平与出血症状具有较强的相关性。Objective To analyze the clinical features and gene mutations types of 15 unrelated probands with coagulation factor V(FV)deficiency,and explore the possible molecular pathogenesis.Methods FV activity(FV:C)and FV antigen(FV:Ag)were detected by one-stage clotting and ELISA,respectively.All 25 exons of the F5 gene in the patients were amplified by PCR,and se-quenced directly.Haplotype analysis was performed with diferent polymorphisms on FV.Protein modeling was applied to analyze the potential molecular mechanisms.Results Of the 5 probands with an FV:C greater than 10%,only 1 had minor bleeding symptoms.In the 10 probands with FV:C less than 10%,seven showed various bleeding manifestations.A total of 12 gene mutations locus were de-tected from 15 probands(8 gene mutations locus were novel mutations,and 1 was pathogenic polymorphism).An in silico analysis pre-liminarily investigated the potential pathogenic mechanism of the mutation.Modeling analysis showed that all the six missense mutations would lead to conformational alterations in the FV protein.Among them,two(p.Ser1781Arg and p.Asp96His)would decrease hydro-gen bonds.Conclusion The level of FV in these probands with inherited FV deficiency were associated with mutations in the respec-tive F5 gene,and the FV levels strongly correlated with the probability of hemorrhage.

关 键 词：凝血因子V缺陷症 临床特征 复合杂合突变 

分 类 号：R446[医药卫生—诊断学]