There was significant overrepresentation of ultra-rare nonsynonymous variants in European SIDS cases (18 of 278 [6.5%]) versus European control subjects (30 of 973 [3.1%]; p = 0.013) when combining all 4 major cardiac channelopathy genes (KCNQ1, KCNH2, SCN5A, and RYR2).
To address these questions, we studied four missense KCNH2 (encoding HERG) variants, one compound KCNH2 genotype, and a missense KCNQ1 mutation all previously identified in Norwegian SIDS cases.
Mutations in HERG and KCNQ1 potassium channels have been associated with Long QT syndrome and atrial fibrillation, and more recently with sudden infant death syndrome and sudden unexplained death.
The LQTS is caused by mutations in genes encoding cardiac ion channels, and mutations in the genes KVLQT1 and SCNA5 have been identified in cases initially diagnosed as SIDS, in addition to several polymorphisms in these 2 genes and in the HERG gene.
We screened genomic DNA from a child who died of SIDS and identified a de-novo mutation in KVLQT1, the gene most frequently associated with long QT syndrome.