The L1786Q mutation is associated with a combined LQT3 and concealed BrS phenotype explained by gating characteristics of the mutated ion channel protein.
SCN5A genetic variants were identified in 14 of the 47 patients with BrS and four of the 14 patients with BrS had missense mutations (1651 G>A, 1776 C>G, 3578 G>A).
Numerous disease‑causing mutations of SCN5A have been identified in patients with ≥10 different conditions, including type 3 long‑QT syndrome and Brugada syndrome.
In LQTS, as in the Brugada syndrome, a mutation in an ion channel gene (in some cases the same gene--SCN5A) is responsible for the development of a large transmural dispersion of repolarization, which serves to provide the arrhythmogenic substrate tha can lead to sudden death.
The reported Brugada syndrome causing mutation R1512W in cardiac sodium channel α subunit encoded gene SCN5A, without obvious loss of function of cardiac sodium channel in previous in vitro study, was identified as the first genetic cause of Chinese SUNDS by us.
We identified 2 compound heterozygous mutations (p.D1690N and p.G1748D) in the SCN5A gene encoding cardiac Na(+) channels (Nav1.5) in a proband diagnosed with Brugada syndrome type 1.
Therefore, ajmaline challenge represents an important step to rule out potential BrS overlap in these patients before starting sodium channel blockers for the beneficial effect of QT shortening in LQT3.
Recently, a novel mutation in the glycerol-3-phosphate dehydrogenase 1-like gene (GPD1-L) disrupted trafficking of SCN5A in a multigenerational family with BrS.
Taken together, we have shown how apparently benign SCN5ABrS mutations can lead to the ECG abnormalities seen in patients with BrS through an induced defect that is only present when the mutations are coexpressed with WT channels.
Prolonged Right Ventricular Ejection Delay in Brugada Syndrome Depends on the Type of SCN5A Variant - Electromechanical Coupling Through Tissue Velocity Imaging as a Bridge Between Genotyping and Phenotyping.
Exploring 66 cardiac genes using a new custom next-generation sequencing panel, we identified a double heterozygosity for pathogenic mutations in SCN5A and TRPM4 in a Brugada syndrome patient.
We found novel mutations in SCN5A in 2 different families diagnosed with Brugada syndrome and investigated how those affected Na(V)1.5 channel function.
The spectrum of phenotypes related to mutations of the SCN5A gene include Brugada syndrome (BS), long QT syndrome, progressive cardiac conduction defect, and sinus node disease (SND).
Our findings indicate that bupivacaine may induce the electrocardiographic and arrhythmic manifestations of the Brugada syndrome in silent carriers of SCN5A mutations.