二代测序技术检测房颤伴高度房室传导阻滞患者致病基因分析  

Genetic screening of a family with atrial fibrillation and high degree atrioventricular block using next generation sequencing

作　　者：杜媛[1] 王娅 韩秀[1] 韩克[1] 马爱群[1] 王亭忠[1] DU Yuan;WANG Ya;HAN Xiu;HAN Ke;MA Aiqun;WANG Tingzhong(Department of Cardiovascular Medicine,First Affiliated Hospital of Xi’an Jiaotong University,Key Laboratory of Molecular Cardiology of Shaanxi Province,Key Laboratory of Environment and Genes Related to Diseases,Ministry of Education,Xi’an Jiaotong University,Xi’an 710061,China)

机构地区：[1]西安交通大学第一附属医院心血管内科,陕西省分子心脏病学重点实验室,环境与疾病相关教育部重点实验室,西安710061

出　　处：《山西医科大学学报》2018年第10期1150-1154,共5页Journal of Shanxi Medical University

基　　金：陕西省重点研发计划-国际科技合作项目(2017KW-065,2018KW-061)

摘　　要：目的利用高通量二代测序技术检测房颤伴高度房室传导阻滞致病基因。方法收集1个房颤伴高度房室传导阻滞家系的临床资料,同时采集外周血进行高通量测序筛查致病基因,发现可疑致病基因后采用多种生物信息学软件预测该突变的致病性。结果发现先证者及其1个女儿均携带心脏缓慢延迟整流钾通道编码基因KCNQ1 c. 407G> T(p. C136F)突变,而家系内其余成员均无该突变。c. 407G> T(p. C136F)突变位于KCNQ1通道的S1段,生物信息学软件预测该突变位点是有害突变,可能通过影响通道蛋白功能而致病。结论采用二代测序技术发现房颤伴高度房室传导阻滞患者携带KCNQ1 c. 407G> T(p. C136F)突变,该突变可能通过影响通道蛋白功能而致病。Clinical data,family histories,ECG and echocardiogram were collected from a family with atrial fibrillation and high degree atrioventricular block.Genomic DNA was extracted from blood sample of the proband,and a gene panel related to hereditary cardiovascular diseases was detected using next generation sequencing.Mutation identified in the proband was confirmed in the family members by Sanger sequencing.The potential pathogenicity of the identified mutation was evaluated by PolyPhen-2,SIFT and Mutation Taster software.Results A c.407G>T(p.C136F)mutation in KCNQ1 gene,which encodes the slow delayed rectifying potassium current,was identified in the proband and one of his daughters.This mutation was located in a high evolutionary conservation area among different species.Bioinformatics results indicated that c.407G>T(p.C136F)mutant probably affected the function of the KCNQ1 protein.Conclusion A c.407G>T(p.C136F)mutant in KCNQ1 gene might be the disease-causing gene mutation in this patient with atrial fibrillation and high degree atrioventricular block by influencing the fuction of KCNQ1 protein.

关 键 词：房颤 房室传导阻滞 KCNQ1 p.C136F突变 二代测序技术 

分 类 号：R541.7[医药卫生—心血管疾病]