Our findings broaden the spectrum of cardiac phenotypes associated with SCN5Achannelopathy, underlining the complex clinical manifestations of genetic variations within this gene.
The genetic test was positive in 12 (26%; 95% CI 15.6-40.3) patients; 10 (21.7%) had PKP2 mutation related to arrhythmogenic right ventricular dysplasia mutation, one (2.2%) KCNQ1 mutation and one (2.2%) SCN5A mutation related to channelopathies.
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.
SCN5A mutations involving the α-subunit of the cardiac voltage-gated muscle sodium channel (NaV1.5) result in different cardiac channelopathies with an autosomal-dominant inheritance such as Brugada syndrome.
This complex protein is encoded by the SCN5A gene that, in its mutated form, is implicated in various diseases, particularly channelopathies, specifically at cardiac tissue level.
Together, the results from this study demonstrate that the SCN5A(E558X/+) pig model accurately phenocopies many aspects of human cardiac sodium channelopathy, including conduction slowing and increased susceptibility to ventricular arrhythmias.
This large-animal model exhibits many phenotypes seen in patients with SCN5A loss-of-function mutations and has the potential to provide important insight into sodium channelopathies.
The notable pathophysiological overlap between familial SSS and Na channelopathy indicates that familial SSS with SCN5A mutations may represent a subset of cardiac Na channelopathy with strong male predominance and early clinical manifestations.
Hundreds of genetic variants in SCN5A, the gene coding for the pore-forming subunit of the cardiac sodium channel, Na(v) 1.5, have been described in patients with cardiac channelopathies as well as in individuals from control cohorts.
This observation confirms the possibility that SCN5A mutations may confer susceptibility for recurrent seizure activity, supporting the emerging concept of a genetically determined cardiocerebral channelopathy.
We report a Korean case of an overlap syndrome of cardiac sodium channelopathy with SCN5Ap.R1193Q polymorphism, treated by the placement of an intrapericardial implantable cardioverter-defibrillator (ICD) at the age of 27 months.
In loss-of-function SCN5Achannelopathies, patients carrying T and M(inactive) mutations develop a more severe phenotype than those with M(active) mutations.
Genetically modified mice rapidly appeared as promising tools for understanding the pathophysiological sequence of cardiac SCN5A-related channelopathies and several mouse models have been established.
Various SCN5A mutations are now known to present with mixed phenotypes, a presentation that has become known as "overlap syndrome of cardiac sodium channelopathy."
The aim of the present study was to elucidate the molecular mechanism underlying the concomitant occurrence of cardiac conduction disease and long QT syndrome (LQT3), two SCN5Achannelopathies that are explained by loss-of-function and gain-of-function, respectively, in the cardiac Na+ channel.
Here, we review the causal link between SIDS and mutations involving the SCN5A-encoded cardiac sodium channel, provide new findings following extensive postmortem genetic testing of long QT syndrome (LQTS)-associated potassium channel genes in a population-based cohort of SIDS, and summarize the current understanding regarding the spectrum and prevalence of cardiac channelopathies in the pathogenesis of SIDS.
Mutations in sodium channel alpha-subunit gene (SCN5A) result in multiple arrhythmic syndromes, including long QT3 (LQT3), Brugada syndrome (BS), an inherited cardiac conduction defect, sudden unexpected nocturnal death syndrome (SUNDS) and sudden infant death syndrome (SIDS), constituting a spectrum of disease entities termed Na+ channelopathies.