EENovel 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

Figures

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  Figure 1. 12-Lead ECG recordings of the proband. (A) The baseline ECG of the proband (10 mm/mV, 25 mm/sec, 62 beats/min) showing a borderline QRS duration of 120 msec, the P-R interval was 184 msec and the QT/QTC was 384/389 msec. (B) ECG monitor strip of a spontaneous onset of ventricular fibrillation recorded in Lead II in a Weixian People's Hospital (Xingtai, China) (10 mm/mV, 25 mm/sec). ECG, electrocardiogram.

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  Figure 2. Dynamic changes of the J wave. (A) At baseline routine ECG during the hospitalization (10 mm/mV, 25 mm/sec, 70 beats/min) exhibited a relatively wide P wave (124 msec) and s wave in the inferior leads. (B) In another ECG (10 mm/mV, 25 mm/sec, 74 beats/min), the J wave appeared in leads II, III and AVF (asterisks) accompanied by newly appearing prolonged S-wave upstroke (arrows). ECG, electrocardiogram.

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  Figure 3. DNA sequence analysis of the proband and schematic representation of the α subunit of the sodium channel. (A) DNA sequence analysis of the proband showing a G base deletion at position 839 of the gene SCN5A, which resulted in the replacement of amino acid cysteine at position 280 by serine followed by a 61 frame-shift amino acids before a premature stop codon. (B) Location of C280Sfs*61 in the predictive topologic structure of the SCN5A channel. Grey circles and zigzag line denote the locations of the mutations.

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  Figure 4. Electrophysiological characterization of Nav1.5 channels. (A) Representative sodium current (INa) recordings of WT, C280Sfs*61 and WT + C280Sfs*61. (B) Current-voltage relationships for WT, C280Sfs*61 and WT + C280Sfs*61 channels. (C) Voltage-dependence of activation for WT (n=8) and WT + C280Sfs*61 (n=10). The line represents a fit to the Boltzmann function GNa=[1+exp(V1/2-V)/κ]-1, where V1/2 and κ are the midpoint and the slope factor, respectively, and GNa=INa(norm)/(V-Vrev), where Vrev is the reversal potential and V is the membrane potential. The results showed the mutant channel had no effect on the steady state activation. (D) Steady-stage inactivation relationships for WT (n=10) and WT + C280Sfs*61 (n=10) fitted with Boltzmann function: Ina=INa-max[1+exp(Vc-V1/2)/κ]-1, where the V1/2 and κ are the midpoint and the slope factor, respectively, and Vc is the membrane potential. and there was no significant difference between WT and WT + C280Sfs*61 channels. All data points are shown as the mean value, and the bars represent the standard error of the mean. WT, wild-type.

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  Figure 5. Representative confocal imaging of WT and mutant channels. Each cell was double-stained by anti-Nav1.5 N-terminal antibody (green) and anti-Nav1.5 C-terminal antibody (red). Cells expressing WT channel showed both of the fluorescence, whereas cells transfected with C280Sfs*61 only exhibited the green fluorescence. Scale bar, 10 µm. WT, wild-type.