A novel mutation in the SCN5A gene is associated with Brugada syndrome

• Published in: Life sciences (1973) 2007-01, Vol.80 (8), p.716-724
• Main Authors: Shin, Dong-Jik, Kim, Eunmin, Park, Sang-Bum, Jang, Won-Cheoul, Bae, Yoonsun, Han, Jihye, Jang, Yangsoo, Joung, Boyoung, Lee, Moon Hyoung, Kim, Sung Soon, Huang, Hai, Chahine, Mohamed, Yoon, Sungjoo Kim
• Format: Article
• Language: English
• Subjects: Adult; Aged; Brugada syndrome; Brugada Syndrome - diagnosis; Brugada Syndrome - genetics; Cell Line; DNA Mutational Analysis; Electrophysiology; Female; Genetic Predisposition to Disease; Genetic Testing; Humans; Male; Middle Aged; Muscle Proteins - genetics; Mutation; NAV1.5 Voltage-Gated Sodium Channel; Patch-Clamp Techniques; Pedigree; Polymerase Chain Reaction; SCN5A; Sodium channel; Sodium Channels - genetics; Transfection
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2006.10.025

Brugada syndrome (BS) is an inherited cardiac disorder associated with a high risk of sudden cardiac death and is caused by mutations in the SCN5A gene encoding the cardiac sodium channel α-subunit (Na v1.5). The aim of this study was to identify the genetic cause of familial BS and characterize the electrophysiological properties of a novel SCN5A mutation (W1191X). Four families and one patient with BS were screened for SCN5A mutations by PCR and direct sequencing. Wild-type (WT) and mutant Na v1.5 channels were expressed in tsA201 cells, and the sodium currents ( I Na) were analyzed using the whole-cell patch-clamp technique. A novel mutation, W1191X, was identified in a family with BS. Expression of the WT or the mutant channel (Na v1.5/W1191X) co-transfected with the β 1-subunit in tsA201 cells resulted in a loss of function of Na v1.5 channels. While voltage-clamp recordings of the WT channel showed a distinct acceleration of Na v1.5 activation and fast inactivation kinetics, the Na v1.5/W1191X mutant failed to generate any currents. Co-expression of the WT channel and the mutant channel resulted in a 50% reduction in I Na. No effect on activation and inactivation were observed with this heterozygous expression. The W1191X mutation is associated with BS and resulted in the loss of function of the cardiac sodium channel.