The sodium channel gene SCN5A and potassium channel genes KCNQ1 and KCNH2 have been widely reported to be genetic risk factors for arrhythmia including Brugada syndrome and long QT syndrome (LQTS).
In this study, we analyzed the genetic variants of KCNQ1, KCNH2, and SCN5A in patients from seven cohorts (total N = 11945, including patients clinically suspected to have inherited arrhythmia [n = 122], other cardiovascular diseases [n = 1045], epilepsy [n = 4797], or other diseases [n = 5841], and healthy controls [n = 140]) who had undergone genetic testing.
Atrial myocyte electrophysiology, Ca<sup>2+</sup> handling, and arrhythmia susceptibility were studied in wild-type and Scn5a knock-in mice expressing phosphomimetic (S571E) or phosphoresistant (S571A) Na<sub>V</sub>1.5 at Ser571.
The major α isoform in the adult human heart is Na<sub>V</sub>1.5, and germline mutations in the Na<sub>V</sub>1.5-encoding gene, sodium voltage-gated channel α subunit 5 (<i>SCN5A</i>), often cause inherited arrhythmias.
We recently reported a quantitative relationship between the degree of functional perturbation reported in the literature for 356 variants in the cardiac sodium channel gene SCN5A and the penetrance of resulting arrhythmia phenotypes.
Mutations and variations in and around SCN5A, encoding the major cardiac sodium channel, influence impulse conduction and are associated with a broad spectrum of arrhythmia disorders.
Individual mutations in the SCN5A-encoding cardiac sodium channel α-subunit usually cause a single cardiac arrhythmia disorder, some cause mixed biophysical or clinical phenotypes.
Impact statement The field of ion channelopathy caused by dysfunctional Nav1.5 due to SCN5A mutations is rapidly evolving as novel technologies of electrophysiology are introduced and our understanding of the mechanisms of various arrhythmias develops.
Mutations disrupting the SCN5A coding sequence cause inherited arrhythmias and cardiomyopathy, and single-nucleotide polymorphisms (SNPs) linked to SCN5A splicing, localization, and function associate with heart failure-related sudden cardiac death.
The purpose of this article was to investigate whether HuR regulates SCN5A mRNA expression and whether manipulation of HuR benefits arrhythmia control in HF.
Aberrant expression of the sodium channel gene (SCN5A) has been proposed to disrupt cardiac action potential and cause human cardiac arrhythmias, but the mechanisms of SCN5A gene regulation and dysregulation still remain largely unexplored.
The authors conducted a retrospective study comprising the 606 patients with LQTS (LQT1 in 47%, LQT2 in 34%, and LQT3 in 9%) who were evaluated in Mayo Clinic's Genetic Heart Rhythm Clinic from January 1999 to December 2015.
Inherited loss-of-function mutations in SCN5A lead to defects in the generation and conduction of the cardiac electrical impulse and are associated with various arrhythmia phenotypes.
Andersen-Tawil syndrome: Clinical presentation and predictors of symptomatic arrhythmias - Possible role of polymorphisms K897T in KCNH2 and H558R in SCN5A gene.