Investigation of epilepsy genes with whole genome approaches

Epilepsy, a rare neurological disease, has a complex etiology that has not been fully elucidated even today. This situation still causes some patients not to be treated despite the developments in the field of medicine in recent years. For this reason, new studies on epilepsy are still of great importance, especially in terms of treating these patients and contributing to the treatment of patients receiving treatment. Recent developments in Next Generation Sequencing (NGS) have revealed a new perspective that can meet this need. Analysis of high-throughput data obtained with Whole Exome Sequencing (WES), one of the NGS methods in the whole genome perspective, has enabled the discovery of pathogenic variants even in complex diseases. In this thesis, 7 individuals in a family, including 3 children, mother, father, aunt and uncle, affected by Familial Adult Myoclonic Epilepsy (FAME) were examined. The segregation of the variants obtained by analyzing the data of the WES study on 3 affected children and their association with epilepsy in the whole family were examined. As a result of the study, some missense variants, which were defined as pathogenic by prediction tools, were detected in the SLC6A19, SCN3A, ADAMTS2, CPO, LAD1, CSF1R and RNF44 genes in the WES data of the 3 siblings. These variants were also screened in other members of the extended family using the Sanger sequencing method and the segregation of the variants was determined. In addition, in terms of the pathogenesis of epilepsy, the genes in which these variants are found are involved in the production and propagation of electrical impulses in neurons, neurotransmitter transport, cellular division, growth or differentiation, etc. It has been determined that they have roles such as the regulation of basic cellular processes. With the findings obtained, it has been revealed that disease-related genes can be detected in complex diseases inherited with different segregation models with the whole genome and exome perspective of NGS methods. This study will be followed by follow-up studies that will examine intronic repeat sequences in the FAME clinic, which stands out with pentamer expansion.