Özet:
Generalized Epilepsy with Febrile Seizures Plus (GEFS+) and Benign Familial Infantile Seizures (BFIS) are some of the benign epilepsy syndromes. GEFS+ is a collection of phenotypes that show febrile seizures beyond the age of six associated with afebrile seizure types. Genotypically, GEFS+ was associated with several ion channel genes such as SCN1A, SCN2A, SCN1B, GABRG2 and GABRD. BFIS is another benign type of idiopathic epilepsy which typically appears on the third month and retracts after the first year. The phenotype overlaps with two other benign syndromes BFNC and BFNIS that differs only in the age of onset. These syndromes are generally inherited in a autosomal dominant manner. To understand the complex nature of epilepsy pathogenesis, the syndromes must be investigated. In this study, the mutational analysis of the two of the candidate genes, SCN1B and SCN2A, was performed on a GEFS+ patient. And the mutational analysis of the candidate genes, SCN1B, KCNQ2 and SCN2A, was performed on the index patient of a multiplex BFIS family. In the GEFS+ patient, a missense mutation was found in the SCN2A gene causing a Ser1536Asn substitution which is evolutionarily conserved in mammals. In the index BFIS, a translationally silent variant c492T>C in the SCN1B gene which co-segregated with the disease in the family was found. This nucleotide change was conserved in the primates and was not polymorphic in the Turkish population. According to the splice site prediction tools, it created a binding site for an enhancer protein and distrupts a silencer motif. However, there was no change in splicing pattern in the mRNA examined from whole blood cells. Although the novel transition in the SCN1B gene could not conclusively be shown to have a causative role in the BFIS phenotype, it deserves further investigation through functional studies since it could be the first mutation in the 19q locus linked to BFIS.
