Epilepsy is one of the most common neurological disorders, affecting people of all ages and causing significant neurobiological, cognitive and psychological consequences. This disorder is characterized by unpredictable seizures associated with abnormal, excessive electrical activity in the brain. The aetiology of epilepsy is varied, ranging from genetic, structural, metabolic and immune causes to infectious and unknown causes. Identifying genetic factors associated with epilepsy is critical because approximately 70–80% of epilepsy cases have genetic components. Advances in next-generation sequencing (NGS) have greatly expanded our understanding of the genetic landscape of epilepsy, identifying more than 1000 genes involved in monogenic forms of the disease. In our pilot study, we conducted the first whole genome sequencing (WGS) in Kazakhstan in 20 child patients diagnosed with epilepsy with seizure onset before the age of three years. Fourteen patients were found to have pathogenic or likely pathogenic variants. This work demonstrates the value of genetic testing in diagnosing epilepsy and determining treatment strategies. This program aims to expand this research by combining whole-exome sequencing (WES) and whole-genome sequencing (WGS) on a broader cohort of pediatric patients with epilepsy and their families. Genetic variants identified will be tested using Sanger sequencing to ensure accuracy. This research has the potential to significantly improve the understanding of genetic epilepsy in Kazakhstan, contributing to the development of personalized treatment protocols, improved patient outcomes, and the development of healthcare and genetic research in the country.

Identification and characterization of the molecular basis of epilepsy in children and families from Kazakhstani populations through combinations of linkage analysis, whole-exome and whole-genome (WES/WGS), and Sanger sequencing

• Clinical and genetic characteristics of the molecular basis of epilepsy in Kazakhstan in children and adults will be obtained. Diagnostic and research work will be carried out.
• Kazakh patients and their families with a treatable genetic defect will undergo testing, and genetically determined treatment will be carried out.
• The effectiveness of carrier testing and prenatal diagnosis in Kazakh families with epilepsy will be assessed, and the diagnosis of patients with a positive history of family relapse, epilepsy and other neurogenetic abnormal phenotypes was improved.
• A unified database of rare genetic mutations and/or common polymorphisms in Kazakhstani populations has been created. Kazakh clinicians and researchers have access to this database.
• The use of next-generation sequencing technology, which will soon allow for the sequencing of the entire exome and genome, is scientifically justified

• Recruited over 30 families with an Epilepsy diagnosis in family history;
• Performed whole-genome sequencing for two families with unique neurological conditions;
• Performed whole-exome sequencing for 40 participants;
• Found seven pathogenic, four likely-pathogenic, and 890 variants of uncertain significance (VUS) in 16 children with epilepsy. Further analysis is ongoing.