Characterization of 13 Novel Genetic Variants in Genes Associated with Epilepsy: Implications for Targeted Therapeutic Strategies

• DOI: 10.1007/s40291-024-00720-2
• Publication Date: 2024-07-14T11:01:11Z
• Authors: Marina Andjelkovic; Kristel Klaassen; Anita Skakic; Irena Marjanovic; Ruzica Kravljanac; Maja Djordjevic; Biljana Vucetic T...; Bozica Kecman; Sonja Pavlovic; Maja Stojiljkovic
• Keywords: Human genetics; Pharmacogenomics

Childhood epilepsies are caused by heterogeneous underlying disorders where approximately 40% of the origins epilepsy can be attributed to genetic factors. The application next-generation sequencing (NGS) has revolutionized molecular diagnostics and enabled identification disease-causing genes variants in childhood epilepsies. objective this study was use NGS identify patients with epilepsy, expand variant spectrum discover potential therapeutic targets. In our study, 55 children unknown etiology were analyzed combining clinical-exome whole-exome sequencing. Novel characterized using various silico algorithms for pathogenicity structure prediction. cause identified 28 overall diagnostic success rate 50.9%. We 22 different associated that correlate well described phenotype. SCN1A gene found five unrelated patients, while ALDH7A1 KCNQ2 twice. other 19 genes, only a single patient. This includes such as ASH1L, CSNK2B, RHOBTB2, SLC13A5, which have recently been epilepsy. Almost half diagnosed (46.4%) carried novel variants. Interestingly, we ALDH7A1, KCNQ2, PNPO, SCN1A, SCN2A resulting gene-directed therapy decisions 11 from including four who all Described will contribute better understanding European landscape, insights into genotype-phenotype correlation worldwide. Given expansion molecular-based approaches, each newly could become target.