BACKGROUND Short-coupled variant of torsades de pointes (scTdP) is a disease characterized by TdP without QT prolongation, which is initiated by extremely short-coupled ventricular extra-systoles. Its genetic background remains rarely unveiled. OBJECTIVE We aimed to identify genetic variations in patients with scTdP and to analyze the functional change of the mutant Na+ channel identified in a scTdP patient. METHODS AND RESULTS We performed genetic analysis for inherited arrhythmia-related 45 genes using next-generation sequencer (MiSeq, Illumina) among seven consecutive scTdP patients. We identified an SCN5A mutation R800H in a 38-year-old male who suffered ventricular fibrillation during dinner and was resuscitated. Two months later, he lost his consciousness at work. His Holter electrocardiogram showed scTdP. He had no family history of sudden cardiac death or heart disease. Functional analysis of the SCN5A-R800H channels showed a significantly shortened recovery time from inactivation. Peak sodium current densities in SCN5A-R800H were larger than those in wild type but the difference was not statistically significant. CONCLUSIONS We identified an SCN5A mutation in a scTdP patient and confirmed that the mutant channel caused the shortness of recovery time from inactivation. SCN5A might be a candidate gene for scTdP.

中文翻译：

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SCN5A突变在尖尖扭转型短耦合患者中鉴定。

背景技术尖端扭转型室间隔短突变（scTdP）是一种以无QT延长的TdP为特征的疾病，其是由极短耦合的室外收缩期引发的。其遗传背景仍然很少被揭露。目的我们旨在鉴定scTdP患者的遗传变异，并分析在scTdP患者中鉴定的突变Na +通道的功能变化。方法和结果我们对连续7位连续的scTdP患者中使用下一代测序仪（MiSeq，Illumina）进行了遗传性心律失常相关的45个基因的遗传分析。我们在一个38岁的男性晚餐中发现了SCN5A突变R800H，该男性在晚餐时出现心室纤颤并被复苏。两个月后，他失去了工作意识。他的Holter心电图显示scTdP。他没有猝死或心脏病的家族病史。SCN5A-R800H通道的功能分析显示，从失活中恢复的时间大大缩短。SCN5A-R800H的钠电流峰值密度大于野生型，但差异无统计学意义。结论我们在scTdP患者中鉴定出SCN5A突变，并证实该突变通道导致了失活恢复时间的缩短。SCN5A可能是scTdP的候选基因。结论我们在scTdP患者中鉴定出SCN5A突变，并证实该突变通道导致了失活恢复时间的缩短。SCN5A可能是scTdP的候选基因。结论我们在scTdP患者中鉴定出SCN5A突变，并证实该突变通道导致了失活恢复时间的缩短。SCN5A可能是scTdP的候选基因。