Exploring the Genetic Etiology of Pediatric Epilepsy: Insights from Targeted Next-Generation Sequence Analysis

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dc.contributor.authorOzturk, Ozden
dc.contributor.authorOzturk, Murat
dc.contributor.authorAtes, Kubra
dc.contributor.authorEsener, Zeynep
dc.contributor.authorErguven, Naile Nisa
dc.contributor.authorOzgor, Bilge
dc.contributor.authorGungor, Serdal
dc.date.accessioned2026-04-04T13:33:17Z
dc.date.available2026-04-04T13:33:17Z
dc.date.issued2025
dc.departmentİnönü Üniversitesi
dc.description.abstractIntroduction: Epilepsy is a group of neurologic disorders with clinical and genetic heterogeneity. Epilepsy often affects children; thus, early diagnosis and precise treatment are vital to protecting the standard of life of a child. Progress in epilepsy-related gene discovery has caused enormous novelty in specific epilepsy diagnoses. Genetic testing using next-generation sequencing is now reachable, leading to higher diagnosis ratios and understanding of the disease's underlying mechanisms. The study's primary aim was to identify the genetic etiology based on targeted next-generation sequence analysis data and to calculate the diagnostic value of the epilepsy gene panel in the 0-17 age-group diagnosed with epilepsy. The secondary aim was to demonstrate the significance of periodic reinterpretation of variant of uncertain significance (VUS) variants and genotype-phenotype correlation. Methods: This retrospective study comprised 107 patients with epilepsy aged 8 months to 17 years, for whom a targeted gene panel covered 110 genes. VUS variants were reanalyzed, and genotype-phenotype correlation was performed. Results: In the initial evaluation, causal variants were described in 23 patients (21.5%). After reinterpretation of VUS, we detected causal variants in 30 out of 107 patients (28%). By reinterpreting the VUS and evaluating genotype-phenotype correlations, we enhanced our diagnostic value by 30.32%. After reinterpretation of VUS variants, the ACMG classification of 36 variants, including 15 benign (31%), 15 likely benign (31%), 5 likely pathogenic (10%), and 1 pathogenic (2%), were redefined. We most frequently detected causal variants in TSC2 (n = 5), GRIN2A (n = 4), and ALDH7A1 (n = 4) genes. Conclusion: The predictive value for epilepsy panel testing was 28% in the cohort. Our study revealed the importance of reanalysis of VUS variants and contributed to enriching the mutation spectrum in epilepsy.
dc.identifier.doi10.1159/000540762
dc.identifier.endpage127
dc.identifier.issn1661-8769
dc.identifier.issn1661-8777
dc.identifier.issue2
dc.identifier.orcid0000-0003-3875-6770
dc.identifier.pmid40176841
dc.identifier.scopus2-s2.0-105003189338
dc.identifier.scopusqualityQ4
dc.identifier.startpage115
dc.identifier.urihttps://doi.org/10.1159/000540762
dc.identifier.urihttps://hdl.handle.net/11616/109053
dc.identifier.volume16
dc.identifier.wosWOS:001304935800001
dc.identifier.wosqualityQ4
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherKarger
dc.relation.ispartofMolecular Syndromology
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.snmzKA_WOS_20250329
dc.subjectEpilepsy
dc.subjectExome sequencing
dc.subjectGenotype-phenotype correlation
dc.subjectNeurodevelopmental disorders
dc.subjectNext-generation sequencing
dc.titleExploring the Genetic Etiology of Pediatric Epilepsy: Insights from Targeted Next-Generation Sequence Analysis
dc.typeArticle

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