title: A missense mutation in the sodium channel β2 subunit reveals SCN2B as a new candidate gene for Brugada syndrome.
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.
authors.affiliation: Cardiovascular Genetics Center, Institut d'Investigació Biomèdica de Girona, Girona, Spain.
authors.forename: Helena
authors.initials: H
authors.lastname: Riuró
authors.forename: Pedro
authors.initials: P
authors.lastname: Beltran-Alvarez
authors.forename: Anna
authors.initials: A
authors.lastname: Tarradas
authors.forename: Elisabet
authors.initials: E
authors.lastname: Selga
authors.forename: Oscar
authors.initials: O
authors.lastname: Campuzano
authors.forename: Marcel
authors.initials: M
authors.lastname: Vergés
authors.forename: Sara
authors.initials: S
authors.lastname: Pagans
authors.forename: Anna
authors.initials: A
authors.lastname: Iglesias
authors.forename: Josep
authors.initials: J
authors.lastname: Brugada
authors.forename: Pedro
authors.initials: P
authors.lastname: Brugada
authors.forename: Francisco M
authors.initials: FM
authors.lastname: Vázquez
authors.forename: Guillermo J
authors.initials: GJ
authors.lastname: Pérez
authors.forename: Fabiana S
authors.initials: FS
authors.lastname: Scornik
authors.forename: Ramon
authors.initials: R
authors.lastname: Brugada
mesh_terms: D053840:Brugada Syndrome / Q000235:genetics*; D016757:Death, Sudden, Cardiac / Q000209:etiology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D020125:Mutation, Missense; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism; D062548:Voltage-Gated Sodium Channel beta-2 Subunit / Q000235:genetics* / Q000378:metabolism
chemical_list: C117620:SCN2B protein, human; D015222:Sodium Channels; D062548:Voltage-Gated Sodium Channel beta-2 Subunit