The implications of genetic mutations in the sodium channel gene (SCN5A)

Abstract

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. These diseases are allelic disorders, if not the same disease with variable penetrance and variable modifiers worldwide. Interestingly, death occurs during sleep in all of these disorders, suggesting a common mechanism. To date, mutational analyses have revealed about 103 distinct mutations in SCN5A, of which at least more than 30 mutations are associated with LQT3, whereas the rest of the mutations are affiliated with the remaining sodium channel disorders. The majority of these mutations are missense. However, other types such as deletions, insertions, frameshifts, nonsense and splice-donor errors have also been reported.