A Missense Mutation in the Sodium Channel 2 Subunit Reveals SCN2B as a New Candidate Gene for Brugada Syndrome

作者：Riuro Helena; Beltran Alvarez Pedro; Tarradas Anna; Selga Elisabet; Campuzano Oscar; Verges Marcel; Pagans Sara; Iglesias Anna; Brugada Josep; Brugada Pedro; Vazquez Francisco M; Perez Guillermo J; Scornik Fabiana S; Brugada Ramon^*

来源：Human Mutation, 2013, 34(7): 961-966.

DOI：10.1002/humu.22328

• Brugada Syndrome
• sudden cardiac death
• SCN5A
• SCN2B

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 2 subunit encoded by SCN2B, in a woman diagnosed with BrS. We studied the sodium current (INa) from cells coexpressing Nav1.5 and wild-type (2WT) or mutant (2D211G) 2 subunits. Our electrophysiological analysis showed a 39.4% reduction in INa density when Nav1.5 was coexpressed with the 2D211G. Single channel analysis showed that the mutation did not affect the Nav1.5 unitary channel conductance. Instead, protein membrane detection experiments suggested that 2D211G decreases Nav1.5 cell surface expression. The effect of the mutant 2 subunit on the INa strongly suggests that SCN2B is a new candidate gene associated with BrS.

• 出版日期2013-7