Clinical Analysis And GABRG2 Genetic Study Of GEFS+ Pedigrees

Generalized epilepsy with febrile seizures is an epileptic syndrome that the children affected with febrile seizures persist febrile seizures after the age of six, and/or afebrile generalized/localized seizures. As a new syndrome, it was classified into idiopathic generalize epilepsy syndrome by the International League of Against Epilepsy(ILAE) in 2001. This familial syndrome is composed of a spectrum of phenotypes including (a)FS; (b)FS+, in which children had seizures with fever in early childhood and continued beyond age 6 years, or were associated with afebrile tonic-clonic seizures; and (c)FS+ with other types of generalized (absence, myoclonic, or atonic) or partial seizures and (d) FS+ with less common and more serious myoclonic astatic epilepsy and severe myoclonic epilepsy of infantile. 10 GEFS+ pedigrees were collected in our Epilepsy Center, and the patients were classified into different types of seizures and syndromes according to the classification criterion of ILAE(2001) and nomenclature of Scheffer and Berkovic. Through analyzing the clinical data of these pedigrees, we found out that 44 patients (25 males and 19 females) had a phenotype compatible with the diagnosis of the GEFS+ syndrome, and the incidence of males and females was epual(x²=0.481, P>0.05). At least two generations were affected. So we can conclude that GEFS+ is autosomal dominant heredity. The frequent phenotypes are FS and FS+. The rare phenotypes include FS+ with absence, FS+ with myoclonic seizures and FS+ with partial seizures. So this syndrome has phenotypic heterogeneity.GEFS+ has obvious genetic characters. Great progress has been made in the research of gene mutations of GEFS+ abroad in recent years revealing that this syndrome is mostly caused by the mutation of genes encoding ion channels, including voltage-gated sodium ion channels SCN1B, SCN1A, SCN2A and ligand-gated chloride ion channel GABRG2, et al. The mutations of GABRG2 have been found include K289M, R43Q, Q351X and the splicing site mutation of introns. The research on the GABRG2 gene mutations of GEFS+ pedigrees is rare in our country, and now we studied GABRG2 gene of 10 GEFS+ pedigrees to reveal the GABRG2 gene distribution in the GEFS+ patients of the Hans in northern China. We draw the venous blood of 10 probands and 1 patient of GEFS+ pedigrees and 2 controls, abstracted DNA, designed primers, and amplify specifically all the exons of GABRG2 (Exonl-Exon9) through PCR, Finally we sequenced the PCR product and analyzed the sequencing results by Blast Software. We did not find any mutation in these genes. We found that there was a single nucleotide polymorphism C/T at the 40^th base in Exon 5. The result of our experiment indicates that the predescribed mutation sites abroad is not common in the patients of the Hans with GEFS+ in northern China, confirming the genetic heterogeneity of idiopathic generalize epilepsy and indicating that the molecular study of complex genetic epilepsy syndromes needs more effort.