A Nonsense SCN5A Mutation Associated with Brugada‐Type Electrocardiogram and Intraventricular Conduction Defects

Mutations of SCN5A, gene‐encoding α‐subunit of cardiac sodium channel, can cause mixed phenotypes of Brugada syndrome (BrS) and cardiac conduction diseases (CCD). We have identified a nucleotide change of SCN5A (4178T > G), which results in a nonsense mutation, L1393X, in a 36‐year‐old Caucasian man who presented with intraventricular conduction delays and BrS‐type electrocardiogram change. To study biophysical characteristics of L1393X‐SCN5A, electrophysiological and immuno‐staining studies were performed using mammalian expression systems. While WT‐SCN5A showed significant currents (93.3 ± 10.6 pA/pF; 1 μg plasmid), L1393X (5 μg) did not generate any significant currents in NIH‐3T3 cells. The cells cotransfected with WT (0.5 μg) and L1393X (0.5 μg) showed approximately 50% current amplitudes compared to the WT (1 μg). Voltage dependency of a steady‐state activation and inactivation was not affected by the cotransfection of L1393X. Immuno‐histochemical stainings demonstrated that L1393X proteins were expressed in the plasma membranes. Our study demonstrated that L1393X‐SCN5A does not form functional channel proteins, which might account for the patient's mixed phenotypes of BrS and CCD.