Key result
A novel loss-of-function SCN5A variant (p.Ile1343Val) was identified in a 42-year-old patient, causing reduced Na+ current and presenting with abnormal repolarization, AF, and reversible cardiomyopathy.
Case Report (n=1)
A novel loss-of-function SCN5A variant (p.Ile1343Val) broadens the known spectrum of SCN5A channelopathies to include a unique combination of abnormal repolarization, AF, LBBB, and reversible cardiomyopathy.
May warrant SCN5A evaluation in AF with cardiomyopathy; extends phenotypic spectrum but remains hypothesis-generating.
A variety of life-threating arrhythmias are caused by mutations in the cardiac voltage-gated sodium channel encoded by the SCN5A gene. In this study, we report a novel loss-of-function SCN5A variant, p.Ile1343Val (c.4027A>G), identified in a 42-year-old proband who presented with an unusual ECG with abnormal repolarization with biphasic T-waves in anteroseptal leads, persistent atrial fibrillation (AF), intermittent left bundle branch block (LBBB), and reversible cardiomyopathy. The patient did not meet the diagnostic criteria for Brugada syndrome, long QT syndrome, or any other known SCN5A-associated phenotype. Characterization of the biophysical properties of the variant by in vitro patch clamp experiments revealed a reduced Na+ current with no effect on the inactivation kinetics of the channel. This loss-of-function of Na+ current could explain the intermittent LBBB as well as the AF. In conclusion, we describe a unique combination of electrical and structural abnormalities associated with a novel SCN5A variant. Our findings broaden the spectrum of cardiac phenotypes associated with SCN5A channelopathy, underlining the complex clinical manifestations of genetic variations within this gene.
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Boddum et al. (2018) conducted a case report in SCN5A channelopathy (n=1). SCN5A variant p.Ile1343Val (c.4027A>G) was evaluated on Biophysical properties of the variant (in vitro patch clamp). A novel loss-of-function SCN5A variant (p.Ile1343Val) was identified in a 42-year-old patient, causing reduced Na+ current and presenting with abnormal repolarization, AF, and reversible cardiomyopathy.
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