title: KCNQ1 gain-of-function mutation in familial atrial fibrillation.
abstract: Atrial fibrillation (AF) is a common cardiac arrhythmia whose molecular etiology is poorly understood. We studied a family with hereditary persistent AF and identified the causative mutation (S140G) in the KCNQ1 (KvLQT1) gene on chromosome 11p15.5. The KCNQ1 gene encodes the pore-forming alpha subunit of the cardiac I(Ks) channel (KCNQ1/KCNE1), the KCNQ1/KCNE2 and the KCNQ1/KCNE3 potassium channels. Functional analysis of the S140G mutant revealed a gain-of-function effect on the KCNQ1/KCNE1 and the KCNQ1/KCNE2 currents, which contrasts with the dominant negative or loss-of-function effects of the KCNQ1 mutations previously identified in patients with long QT syndrome. Thus, the S140G mutation is likely to initiate and maintain AF by reducing action potential duration and effective refractory period in atrial myocytes.
authors.affiliation: Department of Cardiology, Tongji Hospital, and Institute of Medical Genetics, Tongji University, 399 Xin Cun Road, Shanghai 200065, People's Republic of China. drchen@public7.sta.net.cn
authors.forename: Yi-Han
authors.initials: YH
authors.lastname: Chen
authors.forename: Shi-Jie
authors.initials: SJ
authors.lastname: Xu
authors.forename: Said
authors.initials: S
authors.lastname: Bendahhou
authors.forename: Xiao-Liang
authors.initials: XL
authors.lastname: Wang
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Wen-Yuan
authors.initials: WY
authors.lastname: Xu
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: Jin
authors.forename: Hao
authors.initials: H
authors.lastname: Sun
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Su
authors.forename: Qi-Nan
authors.initials: QN
authors.lastname: Zhuang
authors.forename: Yi-Qing
authors.initials: YQ
authors.lastname: Yang
authors.forename: Yue-Bin
authors.initials: YB
authors.lastname: Li
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.forename: Hong-Ju
authors.initials: HJ
authors.lastname: Xu
authors.forename: Xiao-Fei
authors.initials: XF
authors.lastname: Li
authors.forename: Ning
authors.initials: N
authors.lastname: Ma
authors.forename: Chun-Ping
authors.initials: CP
authors.lastname: Mou
authors.forename: Zhu
authors.initials: Z
authors.lastname: Chen
authors.forename: Jacques
authors.initials: J
authors.lastname: Barhanin
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
mesh_terms: D000200:Action Potentials; D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D001281:Atrial Fibrillation / Q000235:genetics* / Q000503:physiopathology; D019556:COS Cells; D002648:Child; D002681:China; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D004562:Electrocardiography; D005260:Female; D006239:Haplotypes; D006325:Heart Atria / Q000503:physiopathology; D006352:Heart Ventricles / Q000503:physiopathology; D006801:Humans; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; D008126:Lod Score; D008133:Long QT Syndrome / Q000235:genetics / Q000503:physiopathology; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009154:Mutation; D020125:Mutation, Missense; D032383:Myocytes, Cardiac / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010375:Pedigree; D015221:Potassium Channels / Q000235:genetics* / Q000502:physiology; D024642:Potassium Channels, Voltage-Gated
chemical_list: C418492:KCNE3 protein, human; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; C059983:potassium channel protein I(sk)