Abstract：
The KCNJ2 gene encodes inward rectifier Kir2.1 channels, maintaining resting potential and cell excitability. Presumably, clinical phenotypes of mutation carriers correlate with ion permeability defects. Loss-of-function mutations lead to QTc prolongation with variable dysmorphic features, whereas gain-of-function mutations cause short QT syndrome and/or atrial fibrillation.
We screened 210 probands with Long QT syndrome for mutations in the KCNJ2 gene. The electrophysiological study was performed for the p.Val93Ile variant in the transfected CHO-K1 cells.
We found three rare genetic variants, p.Arg67Trp, p.Val93Ile, and p.R218Q, in three unrelated LQTS probands. Probands with p.Arg67Trp and p.R218Q had a phenotype typical for Andersen-Tawil (ATS), and the p.Val93Ile carrier had lone QTc prolongation. Variant p.Val93Ile was initially described as a gain-of-function pathogenic mutation causing familial atrial fibrillation. We validated electrophysiological features of this variant in CHO-K1 cells, but no family members of these patients had atrial fibrillation. Using ACMG (2015) criteria, we re-assessed this variant as a variant of unknown significance (class III).
LQT7 is a rare form of LQTS in Russia, and accounts for 1% of the LQTS cohort. Variant p.Val93Ile leads to a gain-of-function effect in the different cell lines, but its clinical appearance is not so consistent. The clinical significance of this variant might be overestimated.
We screened 210 probands with Long QT syndrome for mutations in the KCNJ2 gene. The electrophysiological study was performed for the p.Val93Ile variant in the transfected CHO-K1 cells.
We found three rare genetic variants, p.Arg67Trp, p.Val93Ile, and p.R218Q, in three unrelated LQTS probands. Probands with p.Arg67Trp and p.R218Q had a phenotype typical for Andersen-Tawil (ATS), and the p.Val93Ile carrier had lone QTc prolongation. Variant p.Val93Ile was initially described as a gain-of-function pathogenic mutation causing familial atrial fibrillation. We validated electrophysiological features of this variant in CHO-K1 cells, but no family members of these patients had atrial fibrillation. Using ACMG (2015) criteria, we re-assessed this variant as a variant of unknown significance (class III).
LQT7 is a rare form of LQTS in Russia, and accounts for 1% of the LQTS cohort. Variant p.Val93Ile leads to a gain-of-function effect in the different cell lines, but its clinical appearance is not so consistent. The clinical significance of this variant might be overestimated.
摘要：
KCNJ2基因编码内向整流Kir2.1通道，保持静息电位和细胞兴奋性。大概,突变携带者的临床表型与离子通透性缺陷相关。功能缺失突变导致QTc延长，具有可变的异形特征，而功能获得突变导致短QT综合征和/或心房颤动。
我们筛选了210名长QT综合征的先证者的KCNJ2基因突变。在转染的CHO-K1细胞中对p.Val93Ile变体进行电生理学研究。
我们发现了三种罕见的遗传变异,p.Arg67Trp,p.Val93Ile,和p.R218Q，在三个不相关的LQTS先证中。具有p.Arg67Trp和p.R218Q的前带具有典型的Andersen-Tawil（ATS）表型，p.Val93Ile载体有单独的QTc延长。变异p.Val93Ile最初被描述为导致家族性心房颤动的功能获得性致病性突变。我们在CHO-K1细胞中验证了这种变体的电生理特征，但这些患者的家属没有房颤。使用ACMG(2015)标准，我们将该变异体重新评估为意义未知的变异体(III类).
LQT7在俄罗斯是一种罕见的LQTS，占LQTS队列的1%。变异p.Val93Ile导致不同细胞系中的功能增益效应，但是它的临床表现并不那么一致。这种变异的临床意义可能被高估了。
我们筛选了210名长QT综合征的先证者的KCNJ2基因突变。在转染的CHO-K1细胞中对p.Val93Ile变体进行电生理学研究。
我们发现了三种罕见的遗传变异,p.Arg67Trp,p.Val93Ile,和p.R218Q，在三个不相关的LQTS先证中。具有p.Arg67Trp和p.R218Q的前带具有典型的Andersen-Tawil（ATS）表型，p.Val93Ile载体有单独的QTc延长。变异p.Val93Ile最初被描述为导致家族性心房颤动的功能获得性致病性突变。我们在CHO-K1细胞中验证了这种变体的电生理特征，但这些患者的家属没有房颤。使用ACMG(2015)标准，我们将该变异体重新评估为意义未知的变异体(III类).
LQT7在俄罗斯是一种罕见的LQTS，占LQTS队列的1%。变异p.Val93Ile导致不同细胞系中的功能增益效应，但是它的临床表现并不那么一致。这种变异的临床意义可能被高估了。
