长QT综合征的遗传学研究进展

长QT综合征(LQTS)是一组编码心肌细胞离子通道及相关蛋白基因突变,与恶性心律失常及心脏性猝死密切相关的遗传性心脏离子通道病。目前发现LQTS有17个亚型,共15个致病基因。LQTS主要遗传方式为常染色体显性遗传,以及常染色体隐性遗传,即伴有耳聋的Jervell和Lange-Nielsen综合征。最常见的LQT1、LQT2和LQT3亚型,约占LQTS的80%。LQT1和LQT2致病基因分别为编码心脏缓慢延迟整流钾电流(IKs)通道和快速延迟整流钾电流(IKr)通道α亚基的KCNQ1和KCNH2基因,LQT3致病基因为编码心脏电压门控钠通道(Nav1.5)钠通道α亚基的SCN5A基因。随着高通量测序在临床的广泛应用,LQTS基因诊断阳性率越来越高,对其致病基因和发病机制研究不断深入,有望实现对患者个性化精准诊治。

Advances in genetics of long QT syndrome

Long QT syndrome(LQTS)is a group of inherited cardiac ion channel diseases that are closely related to malignant arrhythmia and sudden cardiac death due to gene mutations encoding the ion channels and related proteins of cardiac myocytes.Currently,there are 17 subtypes of LQTS and 15 pathogenic genes in total.The main genetic pattern is autosomal dominant and autosomal recessive inheritance,namely Jervell and Lange-Nielsen syndrome with deafness.The most common subtypes of LQT1,LQT2 and LQT3 account for about 80%of LQTS.The LQT1 and LQT2 are associated with mutations in KCNQ1 and KCNH2 that code forα-subunit of slow delayed rectifier potassium current(IKs)channel and rapid delayed rectifier potassium current(IKr)channel,respectively.And LQT3 are associated with mutations in SCN5 A that code for Nav1.5 sodium channelα-subunit.With the extensive clinical application of high-throughput sequencing,the positive rate of LQTS gene diagnosis is getting higher and higher,and the in-depth research on pathogenic genes and pathogenesis is expected to realize personalized and accurate diagnosis and treatment of patients.