A novel SCN1A missense mutation causes generalized epilepsy with febrile seizures plus in a Chinese family

► Identified a novel SCN1A mutation responsible to the GEFS+ family. ► The mutation p.Leu193Phe is the first S3/D1 mutation related to GEFS+. ► The substitution may add four hydrogen bonds with adjacent amino acids. Generalized epilepsy with febrile seizures plus (GEFS+) is a common familial epilepsy syndrome, which generally develops in childhood. GEFS+ is caused by mutations in the sodium-channel α1-subunit (SCN1A). In this report, we investigated a Chinese family with an autosomal dominant form of GEFS+. The affected GEFS+ patients in this family displayed significant inter-family clinical heterogeneity. Linkage analysis localized the disease-causing gene to chromosome 2q24, where SCN1A is located. Furthermore, DNA sequencing of the whole coding region of SCN1A revealed a novel heterozygous nucleotide substitution (c.577C>T) causing a missense mutation (p.L193F) in the S3 segment of SCN1A domain D1. Our results expand the spectrum of SCN1A mutations and provide novel insights between the SCN1A mutations and the clinical variations of GEFS+.