A Novel Scn1a Missense Mutation P. Leu193phe Associated With Gefs~+

Febrile seizures( FS) is a common child disease which the incidence is 2%-5% when children under six. Generalized epilepsy with febrile seizures plus (GEFS+) is a subunit of FS. Children with GEFS+ is characterized with features that beyond six years old persist febrile seizures or afebrile seizures which may include other epilepsy forms. GEFS+ is high clinic and genetic heterogeneity and presents with a autosomal dominant genetic forms.Ion-channel genes and associated factors account for lots of responsible genes,of which sodium-channel subunits and gamma-aminobutyric acid receptors are the most common genes.we investigated a GEFS+ Chinese family with a autosomal dominant inherite forms. A clinical diagnose with the pedigree demonstrate that 9 individuals were affected (32 individuals) and distributed into four generations. Linkage analysis demonstrated that the responsible gene is linked with microsatellite marker D2S142,D2S156,D2S2380,D2S382 and D2S2330,then localized the disease-causing gene to Chromosome 24, with a maximum lod score of 3.01(θ=0.00) at D2S2330, where SCN1A harbored nearby. DNA sequence for whole coding region of SCN1A revealed a nucleotide ubstitution of C577 with T, causing a missense mutation L193F of SCN1A. The mutation was found to segregate with GEFS+ in this Chinese family. The mutation located at the s3 segment of domainⅠ, which might alter theα-helix motif of this transmembrane peptide. Further studies for the L193F mutation might offer a better understanding to the function of SCN1A, and the correlation between the genotype of SCN1A and clinical expression of GEFS+.