title: Identification of a KCNE2 gain-of-function mutation in patients with familial atrial fibrillation.
abstract: Atrial fibrillation (AF) is the most common cardiac arrhythmia encountered in clinical practice. We first reported an S140G mutation of KCNQ1, an alpha subunit of potassium channels, in one Chinese kindred with AF. However, the molecular defects and cellular mechanisms in most patients with AF remain to be identified. We evaluated 28 unrelated Chinese kindreds with AF and sequenced eight genes of potassium channels (KCNQ1, HERG, KCNE1, KCNE2, KCNE3, KCNE4, KCNE5, and KCNJ2). An arginine-to-cysteine mutation at position 27 (R27C) of KCNE2, the beta subunit of the KCNQ1-KCNE2 channel responsible for a background potassium current, was found in 2 of the 28 probands. The mutation was present in all affected members in the two kindreds and was absent in 462 healthy unrelated Chinese subjects. Similar to KCNQ1 S140G, the mutation had a gain-of-function effect on the KCNQ1-KCNE2 channel; unlike long QT syndrome-associated KCNE2 mutations, it did not alter HERG-KCNE2 current. The mutation did not alter the functions of the HCN channel family either. Thus, KCNE2 R27C is a gain-of-function mutation associated with the initiation and/or maintenance of AF.
authors.affiliation: Department of Cardiology, Tongji Hospital, Shanghai, China.
authors.forename: Yiqing
authors.initials: Y
authors.lastname: Yang
authors.forename: Min
authors.initials: M
authors.lastname: Xia
authors.forename: Qingfeng
authors.initials: Q
authors.lastname: Jin
authors.forename: Saïd
authors.initials: S
authors.lastname: Bendahhou
authors.forename: Jingyi
authors.initials: J
authors.lastname: Shi
authors.forename: Yiping
authors.initials: Y
authors.lastname: Chen
authors.forename: Bo
authors.initials: B
authors.lastname: Liang
authors.forename: Jie
authors.initials: J
authors.lastname: Lin
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.forename: Ban
authors.initials: B
authors.lastname: Liu
authors.forename: Qinshu
authors.initials: Q
authors.lastname: Zhou
authors.forename: Dongwei
authors.initials: D
authors.lastname: Zhang
authors.forename: Rong
authors.initials: R
authors.lastname: Wang
authors.forename: Ning
authors.initials: N
authors.lastname: Ma
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Su
authors.forename: Kaiya
authors.initials: K
authors.lastname: Niu
authors.forename: Yan
authors.initials: Y
authors.lastname: Pei
authors.forename: Wenyuan
authors.initials: W
authors.lastname: Xu
authors.forename: Zhaopeng
authors.initials: Z
authors.lastname: Chen
authors.forename: Haiying
authors.initials: H
authors.lastname: Wan
authors.forename: Jianmin
authors.initials: J
authors.lastname: Cui
authors.forename: Jacques
authors.initials: J
authors.lastname: Barhanin
authors.forename: Yihan
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000818:Animals; D001281:Atrial Fibrillation / Q000235:genetics*; D001483:Base Sequence; D019556:COS Cells; D002681:China; D002522:Chlorocebus aethiops; D004562:Electrocardiography; D005260:Female; D006801:Humans; D017136:Ion Transport; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020125:Mutation, Missense / Q000235:genetics / Q000502:physiology; D010375:Pedigree; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000235:genetics* / Q000502:physiology; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics*; D017422:Sequence Analysis, DNA; D014162:Transfection
chemical_list: C489619:KCNE2 protein, human; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D011188:Potassium