[Clinical analysis and screening for SCN1A gene mutation in two pedigrees of generalized epilepsies with febrile...

To study the clinical and genetic characteristics of generalized epilepsy with febrile seizures plus (GEFS).

Data of two probands of the disease were collected through outpatient clinic. DNA was extracted from peripheral blood leukocytes using RelaxGene Blood DNA System. Twenty-six exons of SCN1A were amplified by polymerase chain reaction (PCR), the PCR products were screened by denaturing high performance liquid chromatography (DHPLC), then the abnormal fragments were sequenced by Sanger method in order to find the mutations of SCNIA gene.

(1) There were 28 affected individuals in the two families of GEFS+ (14 males and 14 females). Febrile seizures (FS) were present in 7 cases, febrile seizures plus (FS+) in 6 cases, FS+ and absence seizures in 1 case, FS+ and myoclonic seizures in 1 case, uncertain type in 13 cases. No severe phenotype was seen. Bilineal inheritance occured in one GEFS+ family. (2) A samesense mutation (c. 1212A > G) of SCN1A gene was found in the proband and an unaffected individual of pedigree B of GEFS.

(1) GEFS+ is a syndrome with the characteristics of heterogeneous clinical phenotypes; bilineal inheritance suggests the possibility of complex inheritance with additive gene effects. (2) Our study failed to provide evidence supporting a causal relation between the SCN1A mutation and the etiologic gene in the GEFS+ family B, which indicates that GEFS+ has the phenotypic and genotypic heterogeneity.