title: KCNQ1 and KCNH2 mutations associated with long QT syndrome in a Chinese population.
abstract: The long QT syndrome (LQTS) is a cardiac disorder characterized by prolongation of the QT interval on electrocardiograms (ECGs), syncope and sudden death caused by a specific ventricular tachyarrhythmia known as torsade de pointes. LQTS is caused by mutations in ion channel genes including the cardiac sodium channel gene SCN5A, and potassium channel subunit genes KCNQ1, KCNH2, KCNE1, and KCNE2. Little information is available about LQTS mutations in the Chinese population. In this study, we characterized 42 Chinese LQTS families for mutations in the two most common LQTS genes, KCNQ1 and KCNH2. We report here the identification of four novel KCNQ1 mutations and three novel KCNH2 mutations. The KCNQ1 mutations include L191P in the S2-S3 cytoplasmic loop, F275S and S277L in the S5 transmembrane domain, and G306V in the channel pore. The KCNH2 mutations include L413P in transmembrane domain S1, E444D in the extracellular loop between S1 and S2, and L559H in domain S5. The location and character of these mutations expand the spectrum of KCNQ1 and KCNH2 mutations causing LQTS. Excitement, exercises, and stress appear to be the triggers for developing cardiac events (syncope, sudden death) for LQTS patients with KCNQ1 mutations F275S, S277L, and G306V, and all three KCNH2 mutations L413P, E444D and L559H. In contrast, cardiac events for an LQTS patient with KCNQ1 mutation L191P occurred during sleep or awakening from sleep. KCNH2 mutations L413P and L559H are associated with the bifid T waves on ECGs. Inderal or propanolol (a beta blocker) appears to be effective in preventing arrhythmias and syncope for an LQTS patient with the KCNQ1 L191P mutation.
authors.affiliation: Cardiology Division, the People's Hospital of Peking University, Beijing, P. R. China.
authors.forename: Wenling
authors.initials: W
authors.lastname: Liu
authors.forename: Junguo
authors.initials: J
authors.lastname: Yang
authors.forename: Dayi
authors.initials: D
authors.lastname: Hu
authors.forename: Cailian
authors.initials: C
authors.lastname: Kang
authors.forename: Cuilan
authors.initials: C
authors.lastname: Li
authors.forename: Shuoyan
authors.initials: S
authors.lastname: Zhang
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Chen
authors.forename: Xuguang
authors.initials: X
authors.lastname: Qin
authors.forename: Kang
authors.initials: K
authors.lastname: Ying
authors.forename: Yuntian
authors.initials: Y
authors.lastname: Li
authors.forename: Yushu
authors.initials: Y
authors.lastname: Li
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Li
authors.forename: Xin
authors.initials: X
authors.lastname: Cheng
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.forename: Yu
authors.initials: Y
authors.lastname: Qi
authors.forename: Shenghan
authors.initials: S
authors.lastname: Chen
authors.forename: Qing
authors.initials: Q
authors.lastname: Wang
mesh_terms: D027682:Cation Transport Proteins; D002681:China; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins; D000072237:ERG1 Potassium Channel; D004562:Electrocardiography; D051638:Ether-A-Go-Go Potassium Channels; D005192:Family Health; D005260:Female; D006801:Humans; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; D008133:Long QT Syndrome / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D009154:Mutation; D010375:Pedigree; D015221:Potassium Channels / Q000235:genetics*; D024642:Potassium Channels, Voltage-Gated; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG
chemical_list: D027682:Cation Transport Proteins; D004268:DNA-Binding Proteins; C072312:ERG protein, human; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; C092509:KCNH6 protein, human; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D004247:DNA