This region also contains a locus for right ventricular cardiomyopathy (ARVD5) and the cardiac sodium channel gene (SCN5A), mutations that cause isolated progressive cardiac conduction defect (Lenegre syndrome), long-QT syndrome (LQT3), and Brugada syndrome.
Subsequently, two allelic diseases additional to LQT3 were shown to be due to mutations in the same gene, the Brugada syndrome (BrS) and the Lev-Lenegre syndrome (progressive cardiac conduction defect).
The present study shows that the most common phenotype of gene carriers of a BS-type SCN5A mutation is progressive cardiac conduction defects similar to the Lenègre disease phenotype.
Mutations in SCN5A lead to a broad spectrum of phenotypes, including the Long QT syndrome, Brugada syndrome, Idiopathic ventricular fibrillation (IVF), Sudden infant death syndrome (SIDS) (probably regarded as a form of LQT3), Sudden unexplained nocturnal death syndrome (SUNDS) and isolated progressive cardiac conduction defect (PCCD) (Lev-Lenegre disease).
Mutations in SCN5A lead to a large spectrum of phenotypes, including long-QT syndrome, Brugada syndrome, and isolated progressive cardiac conduction defect (Lenègre disease).
In addition, a model for the SCN5A-linked Brugada syndrome and for the inherited Lenègre disease has been established by heterozygous knock-out of Scn5A.
Mutations in the gene-encoding Na(v)1.5, SCN5A, have been associated with a variety of arrhythmic disorders, including long QT, Brugada, and sick sinus syndromes as well as progressive cardiac conduction defect and atrial standstill.
The authors identified mutations in TRPM4--a nonselective cation channel--in a large family with progressive familial heart block type I and showed that these mutations prevented channel internalization (see the related articles beginning on pages 2745 and 2737, respectively).
(Ambulatory Electrocardiographic Monitoring for the Detection of High-Degree Atrio-Ventricular Block in Patients With New-onset PeRsistent LEft Bundle Branch Block After Transcatheter Aortic Valve Implantation [MARE study]: NCT02153307).
We have previously linked hereditary progressive cardiac conduction defect (hereditary Lenègre's disease) to a loss-of-function mutation in the gene encoding the main cardiac Na+ channel, SCN5A.