A Novel SCN5A Variant Associated with Abnormal Repolarization, Atrial Fibrillation, and Reversible Cardiomyopathy
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A Novel SCN5A Variant Associated with Abnormal Repolarization, Atrial Fibrillation, and Reversible Cardiomyopathy. / Boddum, Kim; Saljic, Arnela; Jespersen, Thomas; Christensen, Alex Horby.
In: Cardiology, Vol. 140, No. 1, 2018, p. 8-13.Research output: Contribution to journal › Journal article › peer-review
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T1 - A Novel SCN5A Variant Associated with Abnormal Repolarization, Atrial Fibrillation, and Reversible Cardiomyopathy
AU - Boddum, Kim
AU - Saljic, Arnela
AU - Jespersen, Thomas
AU - Christensen, Alex Horby
PY - 2018
Y1 - 2018
N2 - 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.lle 343Val (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 lossof-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. (C) 2018 S. Karger AG, Basel
AB - 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.lle 343Val (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 lossof-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. (C) 2018 S. Karger AG, Basel
KW - SCN5A
KW - Atrial fibrillation
KW - Cardiomyopathy
U2 - 10.1159/000487475
DO - 10.1159/000487475
M3 - Journal article
C2 - 29635243
VL - 140
SP - 8
EP - 13
JO - Cardiologia
JF - Cardiologia
SN - 0008-6312
IS - 1
ER -
ID: 213164670