Lack of replication of association between scn1a SNP and febrile seizures.

摘要

Febrile seizures (FS) affect 3% of children aged 6 months to 6 years and have a strong genetic component with recurrence risk ratios of 3-5 in first-degree relatives.1 In rare families with autosomal dominant FS, mutations in the sodium channel alpha 1 subunit gene, SCN1A, have been identified.2'3 However, FS usually show complex inheritance with a polygenic basis. The search for susceptibility variants has been slow, so the recent report of a common splice site single nucleotide polymorphism (SNP) in SCN1A (IVS5N + 5 G>A, rs3812718) is notable. Two patient groups were studied: the first, adults with focal epilepsy with and without a history of FS (n = 90 and 486 respectively); the second, children with FS (n = 144). Patients homozygous for the A allele were reported to have a genotype relative risk of ~3.0 for FS.4 The rs3812718 SNP is a plausible candidate for FS as it influences relative expression of neonatal and adult transcripts of SCN1A, which plays a key role in membrane excitability.