A truncating SCN5A mutation combined with genetic variability causes sick sinus syndrome and early atrial fibrillation.

ABSTRACT:

Background

Mutations in the SCN5A gene, encoding the α subunit of the cardiac Na(+) channel, Nav1.5, can result in several life-threatening arrhythmias.

Objective

To characterize a distal truncating SCN5A mutation, R1860Gfs*12, identified in a family with different phenotypes including sick sinus syndrome, atrial fibrillation (AF), atrial flutter, and atrioventricular block.

Methods

Patch-clamp and biochemical analyses were performed in human embryonic kidney 293 cells transfected with wild-type (WT) and/or mutant channels.

Results

The mutant channel expressed alone caused a 70% reduction in inward sodium current (INa) density compared to WT currents, which was consistent with its partial proteasomal degradation. It also led to a negative shift of steady-state

SUBMITTER: Ziyadeh-Isleem A 

PROVIDER: S-EPMC4056672 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature