Academic Journal
Diagnostic yield of chromosomal microarray and virtual targeted gene panel analysis in adults with focal epilepsy: implications for sequential genetic testing strategy.
| Τίτλος: | Diagnostic yield of chromosomal microarray and virtual targeted gene panel analysis in adults with focal epilepsy: implications for sequential genetic testing strategy. |
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| Συγγραφείς: | Panadés-de Oliveira L; Epilepsy Program, Hospital del Mar Research Institute, Barcelona, Spain; Department of Neurology, Hospital del Mar, Barcelona, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain. Electronic address: lpanadesdeoliveira@hmar.cat., Salido Galeote M; Molecular Cytogenetics Laboratory, Department of Pathology, Hospital del Mar, Barcelona, Spain., Prado Duran E; Department of Neurology, Hospital del Mar, Barcelona, Spain., Vilella L; Epilepsy Program, Hospital del Mar Research Institute, Barcelona, Spain; Department of Neurology, Hospital del Mar, Barcelona, Spain., Celdrán de Castro García A; Epilepsy Program, Hospital del Mar Research Institute, Barcelona, Spain; Department of Neurology, Hospital del Mar, Barcelona, Spain., Principe A; Epilepsy Program, Hospital del Mar Research Institute, Barcelona, Spain; Department of Neurology, Hospital del Mar, Barcelona, Spain; Department of Medicine and Life Sciences, Universitat Pompeu Fabra, Barcelona, Spain., Puiggros Metje A; Molecular Cytogenetics Laboratory, Department of Pathology, Hospital del Mar, Barcelona, Spain., Cuscó Martí I; Department of Genetics, Institut de Recerca Sant Pau (IR SANT PAU), Hospital de la Santa Creu i Sant Pau, UAB, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras, Instituto de Salud Carlos III (CIBERER-ISCIII), Spain., Pérez-Jurado LA; Centro de Investigación Biomédica en Red de Enfermedades Raras, Instituto de Salud Carlos III (CIBERER-ISCIII), Spain; Department of Genetics, Hospital del Mar and Hospital del Mar Research Institute, Barcelona, Spain; Department of Medicine and Life Sciences, Universitat Pompeu Fabra, Barcelona, Spain., Zucca R; Epilepsy Program, Hospital del Mar Research Institute, Barcelona, Spain; Department of Neurology, Hospital del Mar, Barcelona, Spain., Boronat S; Department of Genetics, Institut de Recerca Sant Pau (IR SANT PAU), Hospital de la Santa Creu i Sant Pau, UAB, Barcelona, Spain; Department of Genetics, Hospital del Mar and Hospital del Mar Research Institute, Barcelona, Spain., Rocamora R; Epilepsy Program, Hospital del Mar Research Institute, Barcelona, Spain; Department of Neurology, Hospital del Mar, Barcelona, Spain; Department of Medicine and Life Sciences, Universitat Pompeu Fabra, Barcelona, Spain. |
| Πηγή: | Seizure [Seizure] 2026 Apr; Vol. 137, pp. 32-39. Date of Electronic Publication: 2026 Feb 25. |
| Τύπος έκδοσης: | Journal Article; Observational Study |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Elsevier Country of Publication: England NLM ID: 9306979 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1532-2688 (Electronic) Linking ISSN: 10591311 NLM ISO Abbreviation: Seizure Subsets: MEDLINE |
| Imprint Name(s): | Publication: London : Elsevier Original Publication: London : Baillière Tindall, c1992- |
| Ιατρικοί όροι (MeSH): | Genetic Testing*/methods , Epilepsies, Partial*/genetics , Epilepsies, Partial*/diagnosis , Microarray Analysis*/methods, Neurodevelopmental Disorders/genetics ; Humans ; Female ; Adult ; Male ; Retrospective Studies ; Middle Aged ; Young Adult ; DNA Copy Number Variations ; Exome Sequencing |
| Περίληψη: | Introduction: The genetic basis of focal epilepsies is increasingly recognised, yet remains underappreciated in adults. We aimed to assess the diagnostic yield of genetic testing in adults with focal epilepsy and evaluate the optimal testing strategy. Methods: We conducted a retrospective observational study of consecutive adult individuals with focal epilepsy evaluated for a genetic cause at our centre between 2021 and 2023. Chromosomal microarray analysis (CMA), the first-tier test in our algorithm, was performed in all cases. In a subset of CMA-negative individuals, exome sequencing with a virtual targeted gene panel (ES-TGP) was subsequently carried out. Demographic, clinical, and genetic data were reviewed. Results: Ninety-nine individuals were included. CMA identified pathogenic copy number variants (CNVs) in 7 cases (7.1 %). ES-TGP, performed in 69 individuals, detected pathogenic or likely pathogenic variants in 11 (15.9 %). Neurodevelopmental disorders (NDD) and malformations of cortical development (MCD) were significantly associated with positive findings on CMA and ES-TGP, respectively. Conclusions: Genetic testing provides meaningful diagnostic value in adults with focal epilepsy. Testing strategies should consider both patient phenotype and local healthcare system resources. While CMA remains a useful initial tool in settings with limited access to next-generation sequencing (NGS)-base techniques, particularly for individuals with NDD, the higher yield of ES-TGP supports prioritising NGS, especially in individuals with MCD or after negative CMA. Relying solely on CMA may delay or prevent a definitive genetic diagnosis. The lower ES-TGP yield compared to paediatric cohorts likely reflects challenges in segregation analysis in adults. Further data from well-characterised adult cohorts are warranted to refine testing algorithms. (Copyright © 2026 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.) |
| Contributed Indexing: | Keywords: Copy number variants; Genetic testing; Neurodevelopmental disorders; Next-generation sequencing; Sequential testing strategy |
| Entry Date(s): | Date Created: 20260305 Date Completed: 20260710 Latest Revision: 20260803 |
| Update Code: | 20260803 |
| DOI: | 10.1016/j.seizure.2026.02.021 |
| PMID: | 41785580 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1532-2688 |
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| DOI: | 10.1016/j.seizure.2026.02.021 |