Dual variation in SCN5A and CACNB2b underlies the development of cardiac conduction disease without Brugada syndrome.

ABSTRACT:

Background

Inherited loss of function mutations in SCN5A have been linked to overlapping syndromes including cardiac conduction disease and Brugada syndrome (BrS). The mechanisms responsible for the development of one without the other are poorly understood.

Methods

Direct sequencing was performed in a family with cardiac conduction disease. Wild-type (WT) and mutant channels were expressed in TSA201 cells for electrophysiological study. Green fluorescent protein (GFP)-fused WT or mutant genes were used to assess channel trafficking.

Results

A novel SCN5A mutation, P1008S, was identified in all family members displaying first-degree atrioventricular block, but not in unaffected family members nor in 430 reference alleles. Peak P1008S current was 11.77% of WT (P < 0.00

SUBMITTER: Hu D 

PROVIDER: S-EPMC2916871 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature