Dynamic change in ST-segment and spontaneous occurrence of ventricular fibrillation in Brugada syndrome with a novel nonsense mutation in the SCN5A gene during long-term follow-up

Abstract

A 67-year-old male underwent genetic testing under the diagnosis of Brugada syndrome because of recurrent ventricular fbrillation with coincident ST-segment elevation in either right precordial, inferior leads or both since the age of 55 years. Screening of gene mutations using denaturing high-performance liquid chromatography (DHPLC) and direct sequencing identifed a novel nonsense mutation (R179X) of SCN5A in a heterozygous manner. The functional assay for the identifed mutation, using a whole-cell patch clamp in the heterologous expression system, revealed that the nonsense mutation, located in the second transmembrane segment of the frst domain (DI-S2) of the α-subunit, failed to synthesize the complete structure of the cardiac sodium channel, thus causing the non-functional channel. Coding effects by the gene mutation was altered during the 12-year follow-up, which might affect the clinical features of the patient through the ion channel density in the ventricle, dynamics of repolarization abnormality and conduction disturbance.