摘要
目的探究与扩张型心肌病(DCM)发生相关的突变基因位点。方法 2019年12月至2021年6月, 通过"儿童DCM易感基因研究项目"招募DCM患儿6例和健康儿童3例进行前瞻性研究。6例患儿, 年龄4个月~14岁, 其中女5例, 男1例;3例健康儿童, 年龄3~13岁, 其中女2例, 男1例。对研究对象进行全外显子测序, 应用生物信息学方法筛选致病基因, 同时采集对应患儿一级亲属静脉血, 对基因突变所在区域进行一代测序。结果共筛选出4个可能与DCM相关的突变基因位点, 患儿1发现亲联蛋白2(JPH2)基因c.2011-3C>G突变, 受检者为纯合突变(GG), 受检者父母为杂合突变(CG)。患儿1同时发现肌联蛋白(TTN)基因c.G49415A突变, 受检者为纯合突变(AA), 受检者父母为杂合突变(GA)。患儿4发现TTN基因c.G23033A突变, 受检者及受检者父亲为杂合突变(GA), 其母为野生型(GG)。患儿5发现TTN基因c.1697516978del突变, 受检者及受检者父亲为杂合突变(TCTTC/T), 其母为野生型(TCTTC/TCTTC)。结论本研究共发现4个与DCM发病相关的致病基因位点, 丰富了DCM疾病基因谱, 为精准医疗的实施提供了靶点。
Objective To explore the mutational loci associated with the occurrence of dilated cardiomyopathy(DCM).Methods Six children with DCM and 3 healthy children were recruited through the"Children DCM Susceptibility Gene Research Project"for a prospective study from December 2019 to June 2021.Six patients were aged from 4 months to 14 years,including 5 girls and 1 boy.Three healthy children were aged between 3-13 years,including 2 girls and 1 boy.Whole exome sequencing was performed on the research subjects,and the pathogenic genes were identified by bioinformatics methods.At the same time,the venous blood of the first-degree relatives of the corresponding children was collected,and the region with gene mutations was subjected to next-generation sequencing.Results A total of 4 mutational loci that might be related to DCM were identified.Case 1 was found to have a c.2011-3C>G mutation in the jounctophiilin-2(JPH2)gene.The c.2011-3C>G mutation was homozygous(GG)in the child,but heterozygous(CG)in the parents.This child also had a c.G49415A mutation in the titin(TTN)gene.This c.G49415A mutation was homozygous(AA)in the child,but heterozygous(GA)in the parents.Case 4 was found to have a c.G23033A mutation in the TTN gene.The c.G23033A mutation was heterozygous(GA)in both the subject and the father,but a wild type(GG)in the mother.Case 5 was found to have a c.16975_16978del mutation in the TTN gene.The c.16975_16978del mutation was heterozygous(TCTTC/T)in the child and the father,but a wild type(TCTTC/TCTTC)in the mother.Conclusions A total of 4 pathogenic gene loci related to the pathogenesis of DCM are identified in this study.The finding enriches the DCM disease gene spectrum and provides targets for the implementation of precision medicine.
作者
武琼
魏兵
安然
Wu Qiong;Wei Bing;An Ran(Department of Neonatology,Northern Theater General Hospital of Chinese People′s Liberation Army,Shenyang 110016,China;Department of Pediatrics,Lishui Municipal Central Hospital,Lishui 323000,China;North Theater General Hospital,Postgraduate Training Base of Dalian Medical University,Shenyang 110016,China)
出处
《中华实用儿科临床杂志》
CAS
CSCD
北大核心
2022年第19期1486-1489,共4页
Chinese Journal of Applied Clinical Pediatrics
基金
辽宁省科学技术计划项目(2018225070)。
关键词
扩张型心肌病
儿童
全外显子检测
基因突变
Dilated cardiomyopathy
Child
Whole exome detection
Gene mutation
