A Novel SCN5A Variant Causes Temperature-Sensitive Loss Of Function in a Family with Symptomatic Brugada Syndrome, Cardiac Conduction Disease, and Sick Sinus Syndrome.

ABSTRACT:

Introduction

Brugada syndrome (BrS) is an inherited arrhythmia syndrome associated with an increased risk of sudden cardiac death. SCN5A is the most important disease-modifying gene for BrS, but many SCN5A variants have not been functionally characterized. Furthermore, the temperature dependency of SCN5A is only rarely explored in in vitro analyses.

Methods

The clinical phenotype of the affected family was assessed by medical history, ECGs and ajmaline challenge. Whole-cell patch clamp recordings were performed on HEK 293T cells expressing Nav1.5-G1712S, a novel SCN5A variant found in the symptomatic family.

Results

Three male family members had experienced sudden cardiac death, sudden cardiac arrest, and rhythmogenic syncopes. Beside a positive ajmaline challenge wit

SUBMITTER: Sanner K 

PROVIDER: S-EPMC8743901 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature