IndraLab

"Loss-of-function mutations in Scn5a have been associated with BrS (Chen et al., xref ), sick sinus syndrome (SSS; Benson et al., xref ), progressive cardiac conduction defect (PCCD, or Lenègre disease; Schott et al., xref ; Tan et al., xref ; Probst et al., xref ) and overlap disorders between these conditions (Remme et al., xref )."

"Nowadays, numerous variations in 23 genes have been linked to BrS since the first gene SCN5A has been associated with BrS in 1998."

"It has been demonstrated that mutations in SCN5A associated with BrS result in loss-of-function of the current carried by the cardiac type sodium channel (Na v 1.5) xref ."

"In general, SCN5A mutations associated with BrS are “loss-of-function” mutations, leading to reduced Na + channel availability, either through decreased membrane surface channel expression or through altered channel gating properties [ xref , xref ]."

"The fact that other channel gene mutations are associated with BrS and LQT3 suggests that many different channels can be involved in generating one clinical phenotype."

"SCN5A mutations are associated with both BrS and familial atrial fibrillation, progressive cardiac conduction defect, sick sinus syndrome, early repolarization syndrome, dilated cardiomyopathy, and sudden infant death syndrome. xref Furthermore, BrS has been linked to mutations in 18 other genes, but they are rarer."

"Genetic analysis revealed a missense mutation in SCN5A (R1193Q) that had been associated with BrS in a previous study [ xref ] and had been characterized as an LQT3 mutation by Wang et al. [ xref ]."

"Loss-of-function mutations in the cardiac sodium channel gene SCN5A are associated with BrS (Kapplinger et al , xref ), PCCD (3), DCM in combination with atrial and ventricular arrhythmias and conduction disease (McNair et al , xref ), sick sinus syndrome (SSS) (Benson et al , xref ), familial atrial fibrillation (AF) (Darbar et al , xref ), and sudden cardiac infant death syndrome (SIDS) (Klaver et al , xref )."

"It is reported to be more common in Asia than in Western countries, with the estimated prevalence ranging from 1:1000 to 1:10000. xref There are 20 genes associated with BrS, and SCN5A is the major causative one. xref Implantable cardioverter-defibrillator (ICD) is the most effective therapy to prevent SCD, and quinidine, isoproterenol, and catheter ablation are also recommended to reduce the incidence rate of arrhythmic events. xref WPW syndrome is the most common cause of preexcitation, and usually it is presented with supraventricular tachycardia and AF."

"Mutations in SCN5A are associated with both BrS and Lenègre disease (Schott et al., xref )."

"For example, despite carrying the mutation since birth, patients with BrS do not typically develop an arrhythmic phenotype until aged approximately 34–53 years. xref Interestingly, the male predominance of an arrhythmic phenotype is not observed in children with BrS. xref Age-dependent hormonal changes have been proposed to explain the increased risk of spontaneous arrhythmias in men after puberty. xref , xref Moreover, within an individual patient with an SCN5A mutation associated with BrS, phenotypic variability exists in the ECG manifestations of the disease as a function of time."

"BrS is often associated with mutations in SCN5A, encoding Na v 1.5, the α subunit of the major cardiac voltage-gated sodium channel."

"LQTS is typically associated with gain-of-function Na + channel mutations while BrS and ICCD are typically associated with loss-of-function, resulting in reduced I Na ."

"SCN5A mutations associated with BrS are loss-of-function, decreasing Na V 1.5 channel availability or surface expression. xref Loss-of-function mutations have also been found in the CACNA1C -encoded pore-forming subunit of the cardiac Ca V 1.2 L-type Ca 2+ channel. xref , xref In addition, genes associated with BrS include those encoding channel modulators, such as Na + and Ca 2+ channel β subunits and proteins responsible for channel trafficking and targeting within the cardiomyocyte."

"SCN5A mutations are variously associated with LQTS3, BrS, progressive cardiac conduction defect (PCCD), sick sinus node syndrome (SSS), atrial fibrillation (AF), and even dilated cardiomyopathy (DCM) xref ."