Mutations in SCN5A lead to a large spectrum of phenotypes, including long-QT syndrome, Brugada syndrome, and isolated progressive cardiac conduction defect (Lenègre disease).
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).
Compound heterozygosity for mutations (W156X and R225W) in SCN5A associated with severe cardiac conduction disturbances and degenerative changes in the conduction system.
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.
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).
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.
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.
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.