SCN5A mutation identified in a patient with short‐coupled variant of torsades de pointes

Abstract

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 extrasystoles. 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.

Primary Electrical Heart Disease—Principles of Pathophysiology and Genetics

“…Genetic analysis conducted by Touat-Hamici et al [32] showed that RYR2 variant I748F in SPRY1 may be pathogenic, changing the thermal stability of the SPRY1 domain, leading to spontaneous Ca 2+ release and further VA. Other RYR2 variants reported to be associated with scTdP are RyR2-V1024I, RyR-N1151S, RyR2-S4938F, RyR2-M995V, and RyR2-H29D [33][34][35]. Finally, Sonoda et al [36] identified an SCN5A mutation in a patient with scTdP. It should be noted that all variants above require further assessment, whereas currently available data suggest a potential genetic basis for scTdP.…”