A Missense Mutation in the Sodium Channel β2 Subunit Reveals SCN2B as a New Candidate Gene for Brugada Syndrome

Riuró, Helena; Beltran-Alvarez, Pedro; Tarradas, Anna; Selga, Elisabet; Campuzano, Oscar; Vergés, Marcel; Pagans, Sara; Iglesias, Anna; Brugada, Josep; Brugada, Pedro; Vázquez, Francisco M.; Pérez, Guillermo J.; Scornik, Fabiana S.; Brugada, Ramon

Abstract

Brugada Syndrome (BrS) is a familial disease associated with sudden cardiac death. A 20%-25% of BrS patients carry genetic defects that cause loss-of-function of the voltage-gated cardiac sodium channel. Thus, 70%-75% of patients remain without a genetic diagnosis. In this work, we identified a novel missense mutation (p.Asp211Gly) in the sodium β2 subunit encoded by SCN2B, in a woman diagnosed with BrS. We studied the sodium current (INa) from cells coexpressing Nav1.5 and wild-type (β2WT) or mutant (β2D211G) β2 subunits. Our electrophysiological analysis showed a 39.4% reduction in INa density when Nav1.5 was coexpressed with the β2D211G. Single channel analysis showed that the mutation did not affect the Nav1.5 unitary channel conductance. Instead, protein membrane detection experiments suggested that β2D211G decreases Nav1.5 cell surface expression. The effect of the mutant β2 subunit on the INa strongly suggests that SCN2B is a new candidate gene associated with BrS. Brugada Syndrome (BrS) is a familial disease associated mainly to a loss-of-function of the cardiac sodium channel. In this work, we identified a novel missense mutation (p.Asp211Gly) in the sodium β2 subunit encoded by SCN2B, in a woman diagnosed with BrS. Our electrophysiological analysis showed that the β2D211G provoked a reduction in INa density by decreasing Nav1.5 cell surface expression. These results strongly suggest that SCN2B is a new candidate gene for BrS. © 2013 WILEY PERIODICALS, INC.

Citation

Riuró, H., Beltran-Alvarez, P., Tarradas, A., Selga, E., Campuzano, O., Vergés, M., Pagans, S., Iglesias, A., Brugada, J., Brugada, P., Vázquez, F. M., Pérez, G. J., Scornik, F. S., & Brugada, R. (2013). A Missense Mutation in the Sodium Channel β2 Subunit Reveals SCN2B as a New Candidate Gene for Brugada Syndrome. Human Mutation, 34(7), 961-966. https://doi.org/10.1002/humu.22328

• Journal Article Type: Article
• Acceptance Date: Mar 21, 2013
• Online Publication Date: Apr 4, 2013
• Publication Date: 2013-07
• Deposit Date: Apr 1, 2022
• Journal: Human Mutation
• Print ISSN: 1059-7794
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 34
• Issue: 7
• Pages: 961-966
• DOI: https://doi.org/10.1002/humu.22328
• Keywords: Brugada Syndrome; Sudden cardiac death; SCN5A; SCN2B
• Public URL: https://hull-repository.worktribe.com/output/3570083