KCNH2基因变异致2型长QT综合征一个家系的临床及遗传学分析  

Clinical and genetic analysis of a Chinese pedigree affected with Type 2 Long QT syndrome due to variant of KCNH2 gene

作　　者：杨海涛[1] 孙猛[1] 刘静静[1] 陈晓胜 徐锡峥 胡娟[1] 严丽洁 吴金涛[1] Yang Haitao;Sun Meng;Liu Jingjing;Chen Xiaosheng;Xu Xizheng;Hu Juan;Yan Lijie;Wu Jintao(Department of Cardiology,Central China Fuwai Hospital of Zhengzhou University,Fuwai Central China Cardiovascular Hospital,Zhengzhou,Henan 451464,China;Department of Cardiology,Henan University People′s Hospital,Zhengzhou,Henan 450003,China)

机构地区：[1]郑州大学华中阜外医院,阜外华中心血管病医院心内科,郑州451464 [2]河南大学人民医院心内科,郑州450003

出　　处：《中华医学遗传学杂志》2024年第10期1218-1224,共7页Chinese Journal of Medical Genetics

基　　金：河南省医学科技攻关计划(LHGJ20190784)。

摘　　要：目的探讨1个2型长QT综合征(LQTS)家系的临床与遗传学病因。方法选取2019年8月23日就诊于阜外华中心血管病医院的1个2型LQTS家系为研究对象。采集先证者及其父母的外周血样并提取基因组DNA,对先证者进行全外显子组测序(WES),通过功能注释与PPI分析筛选候选变异。针对候选变异进行Sanger测序验证与致病性分析。本研究通过阜外华中心血管病医院医学伦理委员会的审查(伦理号:2019-15)。结果WES检测结果显示先证者携带KCNH2基因c.1478A>G(p.Tyr493Cys)错义变异,经Sanger测序验证该变异遗传自其父亲。根据美国医学遗传学与基因组学学会(ACMG)相关指南,该变异被判定为可能致病性(PM2_supporting+PM5+PP3+PP4)。结论KCNH2基因c.1478A>G(p.Tyr493Cys)变异可能是上述家系患2型LQTS的遗传学病因。ObjectiveTo explore the clinical and genetic etiology of a Chinese pedigree affected with type 2 Long QT syndrome(LQTS).MethodsA pedigree with type 2 LQTS presented at Fuwai Central China Cardiovascular Hospital on August 23,2019 was selected as the study subject.Peripheral blood samples were collected from the proband and her parents.Following extraction of genomic DNA,whole exome sequencing(WES)was carried out for the proband,and candidate variant was screened through functional annotation and protein-protein interaction(PPI)analysis.Sanger sequencing was conducted to verify the pathogenicity of candidate variant.This study was approved by Medical Ethics Committee of the Fuwai Central China Cardiovascular Hospital(Ethics No.2019-15).ResultsWES revealed that the proband has harbored a missense variant of the KCNH2 gene,namely c.1478A>G(p.Tyr493Cys),which was confirmed by Sanger sequencing to have inherited from her father.Based on the guidelines from the American College of Medical Genetics and Genomics(ACMG),the variant was classified as likely pathogenic(PM2_supporting+PM5+PP3+PP4).ConclusionThe KCNH2 gene c.1478A>G(p.Tyr493Cys)variant probably underlay the type 2 LQTS in this pedigree.

关 键 词：2型长QT综合征 全外显子组测序 KCNH2基因 膜电位调节 

分 类 号：R596[医药卫生—内科学]