目标基因捕获测序技术检测1例肥厚型心肌病致病基因突变  

Detection of pathogenic mutation associated with hypertrophic cardiomyopathy by targeted capture and sequencing technique

作　　者：刘旭霞[1] 姜腾勇[2] 郭俊[1] 郑帅[1] 王绿娅[1] 杜杰[1] 

机构地区：[1]首都医科大学附属北京安贞医院,北京市心肺血管疾病研究所,心血管重塑相关疾病教育部重点实验室 [2]首都医科大学附属北京安贞医院,北京市心肺血管疾病研究所心内科,北京100029

出　　处：《临床检验杂志》2014年第5期333-336,共4页Chinese Journal of Clinical Laboratory Science

基　　金：国家自然科学基金(81300074)

摘　　要：目的通过靶向捕获高通量测序技术初步筛查肥厚型心肌病(HCM)致病基因突变。方法收集1例HCM患者临床信息和外周血,并提取基因组DNA,制备DNA全基因组文库。挑选导致HCM的8个候选基因,用GenCap基因序列捕获技术靶向富集该患者外周血DNA候选基因并行高通量测序。通过生物信息学分析筛选致病突变。用Sanger测序来验证相应致病基因突变位点。结果目标基因靶向捕获测序结果经与公共数据库和内部健康人测序数据库对比,发现致病基因突变位点MYBPC3 D770N,该致病基因突变与Sanger测序结果一致。结论用目标基因靶向捕获测序技术可实现对HCM致病基因突变的初步筛查,对HCM的临床基因诊断具有潜在的应用价值。Objective To screen the mutations of pathogenic genes of hypertrophic cardiomyopathy（ HCM） by targeted gene capture and high throughput sequencing technique. Methods The clinical data and the whole blood from a patient with HCM were collected. The genomic DNA was extracted and whole DNA library was prepared. The exomes of 8 HCM-related genes encoding sarcomere protein in the patients were captured by GenCap capture technique and sequenced. The pathogenic mutations were identified by informatics analysis and validated by Sanger sequencing. Results The sequencing results of captured targeted gene mutations were aligned with public database and internal database of healthy individuals and a pathogenic mutation site MYBPC3 D770N which was consistent with the result of Sanger sequencing was found. Conclusion Targeted gene capture and high-throughput sequencing technique could be applied to screen the pathogenic mutations associated with HCM,which may bring potential applicable value for genetic diagnosis of HCM patients.

关 键 词：肥厚型心肌病 突变 靶向捕获 高通量测序 

分 类 号：R541[医药卫生—心血管疾病] R446[医药卫生—内科学]