Mutational analysis of SCN1A gene in Chinese families with generalized epilepsy with febrile seizures plus

Abstract

Objective To investigate the gene mutations of SCN1A in the families with generalized epilepsy with febrile seizures plus (GEFS+ ) and analyze the genotype-phenotype correlations in GEFS+ families. Methods Genomic DNA was extracted from peripheral blood lymphocytes of the probands and other available members in the GEFS+ families.The phenotypes of the affected members were analyzed.The coding regions and flanking intronic regions of the SCN1A gene were screened for mutations using PCR and direct DNA sequencing. Results Two in 17 families(11.76%) were found with novel SCN1A mutations(C142T, S573R), presenting heterozygote missense mutations in exon 3 and exon 11 located in highly conserved region.The above 2 mutations had not been reported.The proband and other affected members in pedigree 1 all carried the mutation(C142T). Their clinical phenotype included febrile seizures(FS) and FS plus(FS+ ) with generalized tonic-clonic seizures and the penetrance rate was about 75.0%(3/4 cases). The phenotype of the proband in pedigree 2 harbored S573R were FS+ with partial seizures and the penetrance rate was about 66.7%(2/3 cases). Conclusions Two novel missense mutations were identified in the GEFS+ families, which were consistent with autosomal dominant inheritance with incomplete penetrance.C142T located in the S6 transmembrane regions at domain D1 and S573R located between S5-S6 segment at domain D4 in the voltage-gated sodium channel.Two families harbored different genetic mutations, in which the affected members had different clinical phenotypes.SCN1A is one of the pathogenic gene in Chinese GEFS+ patients and the genotypes of GEFS+ family is associated with the clinical phenotypes. Key words: Generalized epilepsy with febrile seizures plus; SCN1A gene; Mutation