Identification of a KCNE2 gain-of-function mutation in patients with familial atrial fibrillation.
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.
Yang
Yiqing
Y
Department of Cardiology, Tongji Hospital, Shanghai, China.
Xia
Min
M
Jin
Qingfeng
Q
Bendahhou
Saïd
S
Shi
Jingyi
J
Chen
Yiping
Y
Liang
Bo
B
Lin
Jie
J
Liu
Yi
Y
Liu
Ban
B
Zhou
Qinshu
Q
Zhang
Dongwei
D
Wang
Rong
R
Ma
Ning
N
Su
Xiaoyan
X
Niu
Kaiya
K
Pei
Yan
Y
Xu
Wenyuan
W
Chen
Zhaopeng
Z
Wan
Haiying
H
Cui
Jianmin
J
Barhanin
Jacques
J
Chen
Yihan
Y
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
C489619:KCNE2 protein, human; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D011188:Potassium