Alterations in the SCN5A gene encoding the cardiac sodium channel Nav1.5 have been linked to a number of arrhythmia syndromes and diseases including long-QT syndrome (LQTS), Brugada syndrome (BrS) and dilative cardiomyopathy (DCM), which may predispose to fatal arrhythmias and sudden death. We identified the heterozygous variant c.316A > G, p.(Ser106Gly) in a 35-year-old patient with survived cardiac arrest. In the present study, we aimed to investigate the functional impact of the variant to clarify the medical relevance. Mutant as well as wild type GFP tagged Nav1.5 channels were expressed in HEK293 cells. We performed functional characterization experiments using patch-clamp technique. Electrophysiological measurements indicated, that the detected missense variant alters Nav1.5 channel functionality leading to a gain-of-function effect. Cells expressing S106G channels show an increase in Nav1.5 current over the entire voltage window. The results support the assumption that the detected sequence aberration alters Nav1.5 channel function and may predispose to cardiac arrhythmias and sudden cardiac death.

中文翻译：

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N末端Na _v 1.5通道变异体的特征–心律不齐和猝死的潜在危险因素？

编码心脏钠通道Nav1.5的SCN5A基因的改变与许多心律失常综合征和疾病有关，包括长QT综合征（LQTS），Brugada综合征（BrS）和扩张型心肌病（DCM），这可能会导致致命心律失常和猝死。我们在一名35岁的心脏骤停幸存患者中鉴定了杂合变异体c.316A> G，p。（Ser106Gly）。在本研究中，我们旨在调查该变体的功能影响，以阐明医学上的相关性。突变体以及野生型GFP标记的Nav1.5通道在HEK293细胞中表达。我们使用膜片钳技术进行了功能表征实验。电生理学测量表明，检测到的错义变体改变了Nav1.5通道功能，从而导致功能获得效应。表达S106G通道的单元在整个电压窗口中显示Nav1.5电流增加。结果支持这样一个假设，即检测到的序列异常会改变Nav1.5通道功能，并可能导致心律不齐和心源性猝死。