Key result
SCN5A mutation linked to short-coupled TdP shortens channel recovery from inactivation.
Why the study?
The genetic background of short-coupled variant of torsades de pointes remains rarely unveiled.
Observational (n=7)
The identification of an SCN5A mutation (R800H) that shortens recovery time from inactivation suggests SCN5A may be a candidate gene for short-coupled variant of torsades de pointes.
Answers are grounded in this paper and cite their sources.
Hypothesis-generating; SCN5A-R800H may contribute to short-coupled torsades de pointes in rare cases but should not yet change practice or screening.
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: 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.
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Sonoda et al. (2020) conducted an observational in Short-coupled variant of torsades de pointes (scTdP) (n=7). Genetic analysis (next-generation sequencing) vs. Wild type channel (for functional analysis) was evaluated on Identification of genetic mutations and functional properties of the mutant channel. Genetic analysis of seven patients with short-coupled variant of torsades de pointes identified an SCN5A-R800H mutation in one patient, which caused a significantly shortened recovery time from inactivation.
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