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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Holistic exome-based genetic testing in adults with epilepsy.
Neurol. Genet. 11:e200260 (2025)
Verlagsversion
DOI
PMC
BACKGROUND AND OBJECTIVES: Exome sequencing (ES) is increasingly used in the diagnostic workup of epilepsies. While its utility has been extensively demonstrated in children, its role in adults remains to be defined. In this study, we evaluate the outcomes of a holistic exome-based approach in adults with epilepsy. METHODS: We included 106 adults with epilepsy and a presumed genetic etiology between January 2015 and December 2023 at the Medical University of Vienna, Austria. Diagnostic ES, including copy number variation (CNV) and mitochondrial analyses, was performed. We report on diagnostic outcomes, phenotype expansions, and research findings. Furthermore, we compared the diagnostic outcomes with 3 comprehensive gene panels. RESULTS: In our cohort, the diagnostic yield was 30.2%, outperforming all 3 simulated gene panels. A developmental and epileptic encephalopathy phenotype was associated with receiving a genetic diagnosis. Overall, 27 distinct molecular etiologies were identified. Eight patients had pathogenic CNVs, and 2 had mitochondrial DNA variants. Molecular diagnoses had potential clinical implications in 8 of 32 solved cases (25%), which were eventually exerted in 5 patients (15.6%). Tailored treatment changes were successfully applied in SCN1A-related epilepsy (discontinuation of sodium channel blockers) and GLUT1 deficiency (ketogenic diet). Three patients with mitochondrial diseases were referred for preventive screening investigations after the genetic diagnosis. Our findings expand the clinical spectrum of 3 known epilepsy genes. In addition, explorative variant prioritization identified heterozygous truncating variants in CLASP1 in 2 unrelated patients with focal epilepsy, suggesting it as a candidate gene. DISCUSSION: Our study strongly supports the use of holistic genetic approaches, encompassing CNV and mitochondrial analyses, in adults with epilepsy. Similar to pediatric cohorts, results may inform clinical care. Moreover, we report on phenotype expansions and a candidate gene discovery.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
Variants
ISSN (print) / ISBN
2376-7839
e-ISSN
2376-7839
Zeitschrift
Neurology Genetics
Quellenangaben
Band: 11,
Heft: 3,
Artikelnummer: e200260
Verlag
American Academy of Neurology
Verlagsort
Minneapolis, Minn.
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Neurogenomics (ING)