1. A Missense Mutation in the Sodium Channel β2 Subunit RevealsSCN2Bas a New Candidate Gene for Brugada Syndrome
- Author
-
Helena Riuró, Elisabet Selga, Pedro Brugada, Guillermo J. Pérez, Francisco M. Vázquez, Anna Tarradas, Fabiana S. Scornik, Anna Iglesias, Marcel Verges, Pedro Beltran-Alvarez, Oscar Campuzano, Ramon Brugada, Josep Brugada, and Sara Pagans
- Subjects
Candidate gene ,Sodium ,Mutant ,Mutation, Missense ,chemistry.chemical_element ,Biology ,medicine.disease_cause ,Sodium Channels ,Sudden cardiac death ,Genetics ,medicine ,Humans ,Missense mutation ,Genetic Predisposition to Disease ,Genetics (clinical) ,Brugada Syndrome ,Brugada syndrome ,Mutation ,Voltage-Gated Sodium Channel beta-2 Subunit ,Sodium channel ,Middle Aged ,medicine.disease ,Death, Sudden, Cardiac ,chemistry ,Female - 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 Nav 1.5 and wild-type (β2WT) or mutant (β2D211G) β2 subunits. Our electrophysiological analysis showed a 39.4% reduction in INa density when Nav 1.5 was coexpressed with the β2D211G. Single channel analysis showed that the mutation did not affect the Nav 1.5 unitary channel conductance. Instead, protein membrane detection experiments suggested that β2D211G decreases Nav 1.5 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.
- Published
- 2013
- Full Text
- View/download PDF