Referenced in: none

Automatically associated channels: Nav1.5

Title: 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.

Authors: Mihoko Kawamura, Tomoya Ozawa, Takenori Yao, Takashi Ashihara, Yoshihisa Sugimoto, Takafumi Yagi, Hideki Itoh, Makoto Ito, Takeru Makiyama, Minoru Horie

Journal, date & volume: Circ. J., 2009 Mar , 73, 584-8

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/19075524

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 alpha-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.