Functional characterization of a novel frameshift mutation in the C-terminus of the Nav1.5 channel underlying a Brugada syndrome with variable expression in a Spanish family.

ABSTRACT:

Introduction

We functionally analyzed a frameshift mutation in the SCN5A gene encoding cardiac Na(+) channels (Nav1.5) found in a proband with repeated episodes of ventricular fibrillation who presented bradycardia and paroxysmal atrial fibrillation. Seven relatives also carry the mutation and showed a Brugada syndrome with an incomplete and variable expression. The mutation (p.D1816VfsX7) resulted in a severe truncation (201 residues) of the Nav1.5 C-terminus.

Methods and results

Wild-type (WT) and mutated Nav1.5 channels together with hNavβ1 were expressed in CHO cells and currents were recorded at room temperature using the whole-cell patch-clamp. Expression of p.D1816VfsX7 alone resulted in a marked reduction (≈90%) in peak Na(+) current density compared with WT channels

SUBMITTER: Dolz-Gaiton P 

PROVIDER: S-EPMC3868464 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature