Lu Haoyang, Ding Wen, Xiao Hui, Dai Manyu, Xue Yangcheng, Jia Zhuoran, Guo Jie, Wu Mengzuo, Shen Bing, Zhao Ren
Department of Cardiovascular Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
School of Basic Medical Sciences, Anhui Medical University, Hefei, China.
Front Cardiovasc Med. 2022 Oct 31;9:922335. doi: 10.3389/fcvm.2022.922335. eCollection 2022.
Dysfunction of potassium voltage-gated channel subfamily Q member 1 (KCNQ1) is a primary cause of long QT syndrome type 1 (LQT1). Here, we report a missense mutation P441L in KCNQ1 C-terminus of a 37-year-old woman with severe LQT1 phenotype. Variant P441L transporting to the plasma membrane and interacting with KCNE1 were both markedly decreased, leading to potassium efflux disorder and eventually LQT1. Mutations between the C-terminal helix A and helix B of KCNQ1 have linked with low cardiac event risk, however, we firstly find variant P441L causing a severe LQT1 phenotype with a high risk of cardiac events.
钾离子电压门控通道Q亚家族成员1（KCNQ1）功能障碍是1型长QT综合征（LQT1）的主要病因。在此，我们报告了一名患有严重LQT1表型的37岁女性KCNQ1 C末端的错义突变P441L。变体P441L转运至质膜以及与KCNE1相互作用均显著减少，导致钾外流障碍并最终引发LQT1。KCNQ1 C末端螺旋A和螺旋B之间的突变与低心脏事件风险相关，然而，我们首次发现变体P441L会导致具有高心脏事件风险的严重LQT1表型。
