CHARACTERIZATION OF 16 NOVEL GENETIC VARIANTS IN GENES RELATED TO CHILDHOOD EPILEPSIES

Background: Childhood epilepsies are caused by heterogeneous underlying disorders where approximately 40% can be attributed to genetic factors. Application of next-generation sequencing (NGS) has revolutionized diagnostics and therefore has enabled the identification of disease-causing genes and variants in childhood epilepsies. Materials and Methods: Patients who presented with epilepsy of unknown etiology in childhood, with suspicion of a genetic cause were included in this study. In total, 55 patients from unrelated non-consanguineous families were included and analyzed by NGS either using clinical-exome sequencing (MiSeq, Illumina) or whole-exome sequencing (DNBSEQ-G400, MGI). Variants were prioritized using Variant Interpreter and VarSome and classified according to the ACMG recommendations. Results: Using CES we analyzed 38 patients, and for 22 of them a diagnosis was established. Using WES we analyzed 17 patients with childhood epilepsy, which led to the identification of disease-causing genes in 11 patients. The diagnostic success rate for CES was 55.3% (21/38) and the diagnostic rate for WES was 64.7% (11/17), with the overall diagnostic rate being 58.2% (32/55). For these patients, we detected pathogenic, likely pathogenic variants or VUS in 24 epilepsy genes that correlate well to the observed phenotype. Sixteen novel genetic variants were identified and characterized using various in silico algorithms. Conclusion: This is the first study reporting the molecular-genetic basis of childhood epilepsy in Serbia. The prompt establishment of a specific diagnosis is essential in order to make available the prognosis, optimize therapy, and enable counseling on recurrence risk in future pregnancies.ABSTRACT BOOK: “Genetic Diseases from Diagnostics to Prevention and Therapy” October 05-14th Balkan Congress of Human Genetics & 9th Rare Disease SEE Meeting 2023; Skopje, October 05-07, 202