Mutations in the SCN5A gene: evidence for a link between long QT syndrome and sudden death?

Nadine Kiehne, Silke Kauferstein

Forensic Sci Int Genet, 2007 Jun , 1, 170-4

Mutations in cardiac ion channel genes leading to channel dysfunctions or changes in the gene expression may cause inherited arrhythmogenic diseases. These genetic diseases are important causes of sudden unexplained death (SUD). Ten cases of SUD, including six cases of sudden infant death syndrome (SIDS) and four cases of SUD from people in the age of 14-40 years were examined by postmortem molecular analysis. Genomic DNA was extracted from blood cells and two long QT syndrome relevant genes, SCN5A encoding the alpha-subunit of the voltage-gated sodium channel Nav1.5 and KCNH2 encoding the alpha-subunit of the voltage-gated potassium channel HERG were selected for mutation analysis by complete gene sequencing. Various silent mutations in the KCNH2 and SCN5A genes as well as the known H558R polymorphism in SCN5A were detected. Moreover, sequence variations in the 3' untranslated region (3'UTR) and 5' untranslated region (5'UTR) of the SCN5A gene were observed. This study suggests that these areas are important regions to investigate the impact of changes in cardiac ion channel function on the risk of sudden unexpected death.