Novel SCN5A frame-shift mutation underlying in patient with idiopathic ventricular fibrillation manifested with J wave in inferior lead and prolonged S-wave in precordial lead

Mutations in the SCN5A gene has been recognized as resulting in a series of life-threatening arrhythmias. However, it also causes idiopathic ventricular fibrillation (IVF) with J wave in inferior leads and prolonged S-wave upstroke in precordial leads, which has not been previously reported. The present study aimed to study the mechanisms of a patient with IVF manifested with J wave in inferior leads and prolonged S-wave upstroke in precordial leads. The electrocardiograms (ECG) of the proband were recorded and genetic testing was conducted. Patch-clamp and immunocytochemical studies were performed in heterologously transfected 293 cells. The VF attacks was documented in a 55-year-old male proband with syncope episodes. 12-lead ECG shown the transient J wave in the inferior leads and prolonged S-wave upstroke in precordial V1-V3 leads in the same timeframe. Genetic analysis revealed a novel 1 base deletion (G) at position 839 in exon 2 in SCN5A gene (C280S*fs61), which causes a severe truncation of the sodium channel. The functional study revealed that in 293 cells transfected with mutant channel, no sodium current could be recorded even though the immunocytochemical experiment confirmed the truncated sodium channel existed in cytosol. The kinetics of the wild-type (WT) channel were not altered when co-transfected with C280S*fs61 mutant which suggested a haploinsufficiency effect of sodium channel in the cells. The present study identified a novel C280Sfs*61 mutation that caused the 'loss of function' of the sodium channel by haploinsufficiency mechanism. The reduced sodium channel function in the heart may cause conduction delay that may underlie the manifestation of J wave and prolonged S-wave upstroke associated with IVF.

Automated summary

Mutations in the SCN5A gene have been found to cause life-threatening arrhythmias, and they can also lead to idiopathic ventricular fibrillation with J wave in inferior leads and prolonged S-wave upstroke in precordial leads. This study aimed to investigate the mechanisms of a patient with these manifestations by recording electrocardiograms, conducting genetic testing, and performing patch-clamp and immunocytochemical studies.