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A Missense Mutation in the Sodium Channel β2 Subunit Reveals SCN2B as a New Candidate Gene for B rugada Syndrome
Author(s) -
Riuró Helena,
BeltranAlvarez 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
Publication year - 2013
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.22328
Subject(s) - missense mutation , brugada syndrome , sodium channel , nav1.5 , biology , mutant , mutation , protein subunit , gene , genetics , microbiology and biotechnology , sodium , chemistry , neuroscience , organic chemistry
B rugada S yndrome ( B r S ) is a familial disease associated with sudden cardiac death. A 20%–25% of B r S 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 B r S . We studied the sodium current ( I Na ) from cells coexpressing Na v 1.5 and wild‐type (β2WT) or mutant (β2D211G) β2 subunits. Our electrophysiological analysis showed a 39.4% reduction in I Na density when Na v 1.5 was coexpressed with the β2D211G. Single channel analysis showed that the mutation did not affect the Na v 1.5 unitary channel conductance. Instead, protein membrane detection experiments suggested that β2D211G decreases Na v 1.5 cell surface expression. The effect of the mutant β2 subunit on the I Na strongly suggests that SCN2B is a new candidate gene associated with BrS.