期刊
HUMAN MUTATION
卷 34, 期 7, 页码 961-966出版社
WILEY
DOI: 10.1002/humu.22328
关键词
Brugada Syndrome; sudden cardiac death; SCN5A; SCN2B
资金
- Instituto de Salud Carlos III [FI09/00336, CD09/00055, CD10/00275, CD11/00063, PI2008/1800]
- Universitat de Girona [BR2012/47]
- CNIC [CNIC-03-2008]
- Spanish Ministry of Health [Red Cooperativa de Insuficiencia Cardiaca (REDINSCOR)] [RD06/03/0018]
- Sociedad Espanola de Cardiologia
- Obra Social La Caixa
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.
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