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 fibrillation 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 identified a novel nonsense mutation (R179X) of SCN5A in a heterozygous manner. The functional assay for the identified 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 first 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. (Circ J 2009; 73: 584 -588)

Cardiac Channelopathies and Sudden Death: Recent Clinical and Genetic Advances

“…Pathogenic variants in KCNJ8 or ABCC9 may result in a severe arrhythmic phenotype typical of BrS [44]. Mutations in KCNH2 have mainly been associated with LQTS; however, a few pathogenic variants have also been reported in patients with a short-QT interval and Brugada ECG [45,46]. …”

First report of genetic variants detected in Argentinian patients with clinical Long QT Syndrome diagnosis

“…R34C is a frequent polymorphism of this gene and is a relatively common in the black population, although it has also been detected among Hispanics 32 . c.537C>T (p.R179*) variant in SCN5A has been previously reported in individuals with Brugada syndrome and with long QT syndrome [33][34][35] . This variant leads to a premature termination codon at position 179, which is expected to result in an absent or nonfunctional protein.…”

Inducibility of ventricular arrhythmias after gastric distension: The catecholamine equivalent in Brugada syndrome ablation?

“…As previously reported for this patient, 3 genetic testing was positive for a nonsense SCN5A mutation (R179X), which has been found to be associated with a Brugada ECG pattern in the inferior/right precordial leads and produces a nonfunctional cardiac sodium channel, carrying a more severe arrhythmic phenotype. 4 Accordingly, despite antiarrhythmic therapy with quinidine, our patient experienced recurrent appropriate ICD interventions (until February 2013, 11 isolated ICD shocks and 1 arrhythmic storm). Episodes are often preceded by a large meal, and the patient describes the subjective feeling of repetitive palpitations right before the shock.…”