二代测序技术筛查肥厚型心肌病伴房颤家系致病基因研究  

Screening pathogenic gene mutation of a family with hypertrophic cardiomyopathy and atrial fibrillation using next generation sequencing

作　　者：杜媛[1] 罗玲[1] 王娅 韩秀[1] 韩克[1] 马爱群[1] DU Yuan;LUO Ling;WANG Ya;HAN Xiu;HAN Ke;MA Ai-qun(Department of Cardiovascular Medicine,The 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 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,陕西西安710061

出　　处：《西安交通大学学报（医学版）》2018年第6期922-926,共5页Journal of Xi’an Jiaotong University（Medical Sciences）

基　　金：陕西省重点研发计划-国际科技合作项目(No.2017KW-065,2018KW-061)。

摘　　要：目的对1个肥厚型心肌病伴房颤先证者及其家系成员进行致病基因筛查研究。方法收集先证者及其家系成员外周血,提取基因组DNA,应用二代测序法对先证者进行心血管疾病候选基因突变检测。发现可疑致病位点后,进一步通过Sanger测序法在家系内其他成员以及100个健康个体者中进行验证。用PolyPhen-2等生物信息学软件对新突变位点进行致病突变分析。家系资料收集包括临床表现、体格检查、心电图、超声心动图。结果先证者及家系内多个成员均携带PRDM16基因c.3124G>A(p.G1042R)杂合突变,但先证者父母及100例健康个体中并未发现该突变,因此,该突变可能为新生突变(生殖细胞嵌合)。生物信息学分析结果显示PRDM16基因c.3124G>A(p.G1042R)杂合突变位于保守位点,可能影响蛋白功能,为致病性突变。结论本研究发现1个肥厚型心肌病伴房颤的家系中存在PRDM16基因c.3124G>A(p.G1042R)杂合突变,该突变所在区域在不同种系间高度保守,可能是该肥厚型心肌病家系的致病基因突变位点。Objective To identify a potential pathogenic gene mutation among a family with hypertrophic cardiomyopathy(HCM)and atrial fibrillation(AF).Methods Clinical data,family history,ECG,and echocardiogram were collected from the proband as well as family members.Genomic DNA was extracted from blood sample,and a gene panel related to hereditary cardiovascular diseases was detected using next-generation sequencing.Mutation identified in the proband was confirmed by Sanger sequencing in other family members and 100 healthy controls.The potential pathogenicity of the identified mutation was assessed by PolyPhen-2,SIFT and Mutation Taster software.Results Three patients showed clinical symptoms related to the pathology.A novel PRDM16 gene c.3124G>A(p.G1042R)mutation was identified in the proband and several members in this family.However,this mutation was not found in the proband s parent and the healthy controls,so it could be a de novo mutation.This mutation was located in a high evolutionary conservation area among different species.Both conservatism and bioinformatics results indicated that the mutation probably had affected the function of the protein.Conclusion The novel missense mutation of PRDM16 gene c.3124G>A might be the disease-causing gene mutation in this Chinese pedigree with familiar HCM and AF.

关 键 词：肥厚型心肌病 房颤 二代测序 PRDM16基因 突变 

分 类 号：R541.7[医药卫生—心血管疾病]