肥厚型心肌病家系携带ACTN2、MYBPC3和TNNI3基因突变分析  

Mutation analysis of ACTN2,MYBPC3 and TNNI3 genes in families with hypertrophic cardiomyopathy

作　　者：张智文 王婷[2] 杨海涛[2] ZHANG Zhiwen;WANG Ting;YANG Haitao(Henan University People's Hospital,Zhengzhou,450003,China;Heart Center of Henan Province People's Hospital,Central China Fuwai Hospital)

机构地区：[1]河南大学人民医院,郑州450003 [2]河南省人民医院心脏中心华中阜外医院

出　　处：《临床心血管病杂志》2020年第2期166-169,共4页Journal of Clinical Cardiology

基　　金：河南省科技计划项目(No:182102310175).

摘　　要：目的:对收集的1例肥厚型心肌病家系的致病基因进行突变位点分析,阐明基因型与临床表型的关系。方法:利用目标外显子捕获技术和二代测序技术对先证者的与肥厚型心肌病有关的基因进行基因突变筛查,并使用Sanger测序法验证可疑突变位点,同时筛查患者家系成员4例和健康人100例,确定该家系患者的致病突变,并利用SIFT、Polyphen2和MutationTaster这3种软件进行突变基因功能检测。结果:该家系除先证者外,4例有血缘关系的研究对象中3例携带ACTN2基因c.1162T>A错义突变(p.Trp388Arg),2例携带MYBPC3基因c.472G>A错义突变(p.Val158Met),2例携带TNNI3基因c.235C>T错义突变(p.Arg79Cys)。该家系的先证者同时携带上述3种突变基因。3种预测软件预测这3种突变均为有害突变。结论:在该患者家系中发现的基因突变位点可能是肥厚型心肌病的致病突变,携带多种突变的家系成员更易发生肥厚型心肌病,但其确切发病机制仍需进一步研究。Objective:To analyze the mutation sites of pathogenic genes in a family with hypertrophic cardiomyopathy and to elucidate the relationship between genotypes and clinical phenotypes.Method:The gene mutations associated with hypertrophic cardiomyopathy in the proband were screened by target exon capture and second-generation sequencing.In addition,suspicious mutation sites were identified by Sanger sequencing.Four family members and 100 healthy persons were screened to identify the pathogenic mutations in the proband.Last,the function of mutant gene was detected by SIFT,Polyphen2 and Mutation Taster software.Result:Among the 4 related subjects in this family,3 carried c.1162 T>A missense mutation(p.Trp388 Arg)of ACTN2 gene,2 carried c.472 G>A missense mutation(p.Val158 Met)of MYBPC3 gene,and 2 carried c.235 C>T missense mutation(p.Arg79 Cys)of TNNI3 gene.The proband of this family carried the 3 mutation genes at the same time.Three prediction software predicted that all 3 mutations were harmful.Conclusion:The gene mutation found in this patient’s family may be the pathogenic mutation of hypertrophic cardiomyopathy.Family members carrying multiple mutations are more likely to develop hypertrophic cardiomyopathy,but the exact pathogenesis still needs further study.

关 键 词：肥厚型心肌病 家族 基因型 突变 基因检测 

分 类 号：R542.2[医药卫生—心血管疾病]