oa Gene Identification in Autosomal Recessive Forms of Familial Epilepsy

Background: Epilepsy is a disorder of the brain characterized by an enduring predisposition to generate recurrent epileptic seizures, as well as, the neurobiologic, cognitive, psychological, and social consequences. The estimated proportion of the general population with active epilepsy at a given time is 10 per 1,000 people. The cause of epilepsy remains unknown in a substantial proportion of affected individuals. There is considerable evidence of the role of genetics in the predisposition to epileptic seizures. There is a need to identify the genes that predispose to epilepsy.

Objectives: The objective of this study is to attempt at the identification of the genes responsible for specific forms of familial epilepsy by using homozygosity mapping and mutation detection analyses.

Methods: In this study we recruit families in which epilepsy segregates in a suggested autosomal recessive pattern. Homozygosity mapping is applied after genotyping with 370K SNP chips (Illumina platform). The gene identification is performed by candidate gene approach and direct resequencing.

Results: We recruited a consanguineous two-generation family with five affected individuals from two related sibships. All patients were clinically diagnosed and the clinical picture delineated. The gene responsible for the epilepsy in this family has been mapped to a 10 MB region on chromosome 11. At least 10 candidate genes, including SHANK2, SYT12, CFL1 and KCNK4 were examined for mutations but no specific mutations were identified as of yet.

Conclusion: Further examination of other candidate genes is ongoing. However, genomic sequencing utilizing next-generation sequencing technology is in progress.