ABSTRACT
Objective To analyze the phenotypes and to identify SCN1A gene mutation in families with generalized epilepsy accompanied by febrile seizures (GEFS+). Methods The clinical data were collected, and genomic DNA was extracted from peripheral blood lymphocytes of the proband and available members in the GEFS+ families. The phenotypes of the related 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 Thirty-three related members from 10 GEFS+ families, ranged from 2 to 7 members in each family received the examination. T heir phenotypes included febrile seizures (FS) in 11 persons (33.3%), febrile seizures plus (Fs+) in 11 (33.3%), FS with partial seizures in 1 (3.0%), afebrile generalized tonic-clonic seizures (AGTCS) in 3 (9.1%), Dravet syndrome in 1 (3.0%), childhood absence epilepsy in 1 (3.0%), and unclassified seizures in 5 members (15.2%). SCN1A mutations were found in 3 families, including one family with missense mutation (glu1444-lys), and silent mutation: synonymous mutation existed in exon 15 (c.2592G>A), with synonymous mutation in exon 9 (c.1212 G>A) and exon 26 (c.5385 G>A) in two families. Conclusions A new missense mutation and three synonymous mutation have been found in the coding regions of SCN1A gene in three families. One of the families has synonymous mutation in two exons. Genetic mechanism is complicated in GEFS families.