Academic Journal
Diagnostic yield and copy number variants findings in 219 adult patients with developmental and epileptic encephalopathy.
| Τίτλος: | Diagnostic yield and copy number variants findings in 219 adult patients with developmental and epileptic encephalopathy. |
|---|---|
| Συγγραφείς: | Licchetta L; IRCCS Istituto Delle Scienze Neurologiche di Bologna, full member of European Reference Network EpiCARE, Bologna, Italy.; Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy., Bruschi G; Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy., Giangregorio T; Medical Genetics Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy., Stipa C; IRCCS Istituto Delle Scienze Neurologiche di Bologna, full member of European Reference Network EpiCARE, Bologna, Italy., Mannini E; Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy., Minardi R; IRCCS Istituto Delle Scienze Neurologiche di Bologna, full member of European Reference Network EpiCARE, Bologna, Italy., Mostacci B; IRCCS Istituto Delle Scienze Neurologiche di Bologna, full member of European Reference Network EpiCARE, Bologna, Italy., Tontini V; IRCCS Istituto Delle Scienze Neurologiche di Bologna, full member of European Reference Network EpiCARE, Bologna, Italy., Pippucci T; Medical Genetics Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy., Bisulli F; IRCCS Istituto Delle Scienze Neurologiche di Bologna, full member of European Reference Network EpiCARE, Bologna, Italy.; Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy., Magini P; Medical Genetics Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy. |
| Πηγή: | Epilepsia [Epilepsia] 2026 Sep; Vol. 67 (9), pp. e141-e149. Date of Electronic Publication: 2026 Jul 04. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Blackwell Science Country of Publication: United States NLM ID: 2983306R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1528-1167 (Electronic) Linking ISSN: 00139580 NLM ISO Abbreviation: Epilepsia Subsets: MEDLINE |
| Imprint Name(s): | Publication: Malden, MA : Blackwell Science Original Publication: Copenhagen : Munskgaard |
| Ιατρικοί όροι (MeSH): | DNA Copy Number Variations*/genetics , Epilepsy*/genetics , Epilepsy*/diagnosis, Humans ; Female ; Adult ; Male ; Comparative Genomic Hybridization ; Young Adult ; Middle Aged ; Adolescent ; Polymorphism, Single Nucleotide ; Exome Sequencing |
| Περίληψη: | In a clinical setting, exome sequencing (ES) with copy number variant (CNV) analysis is currently the most effective approach for developmental and epileptic encephalopathies (DEE). However, trio-based ES is often not feasible in adults, its costs remain prohibitive in certain health care settings, and computational tools for CNV calling still lack sufficient accuracy. Chromosomal microarray (CMA) is indicated as a first-tier test for CNV detection in patients with DEE, dysmorphisms, and comorbidities. We investigate the role of CNVs in the etiology of DEE in an adult cohort, to define the most appropriate diagnostic approach in this population. A total of 219 patients (male/female: 104/115) with undiagnosed DEE underwent array-based comparative genomic hybridization/single nucleotide polymorphism arrays as adults. Causative CNVs were identified in 18 patients (8.2%); 14 were deletions (mean size ≈ 2.96 Mb), and four were duplications/triplications (mean size ≈ 3.63 Mb). Thirteen were responsible for known deletion/microduplication syndromes, and four were deletions involving haploinsufficient genes associated with epilepsy/neurodevelopmental disorders. For one deletion, population evidence, reports with overlapping deletions, and clinical databases support a likely pathogenic role. The mean age at CMA diagnosis was 32.4 ± 13 years. An additional 46 patients (21%) then received a molecular diagnosis through alternative approaches. Despite a diagnostic delay of 24.2 ± 14.5 years, CMA enabled a genetic diagnosis in 8.2% of our adult DEE patients, especially in those with dysmorphisms. The diagnostic yield rises to 10.4% when excluding patients diagnosed using other methods. A total of 66.7% of solved cases had direct implications from the diagnosis, supporting the clinical utility of CNV analysis inclusion in the diagnostic workflow for adult patients with DEE. (© 2026 The Author(s). Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.) |
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| Grant Information: | Ministero della Salute |
| Contributed Indexing: | Keywords: SNP array; adults; array CGH; developmental and epileptic encephalopathies; microarray |
| Entry Date(s): | Date Created: 20260704 Date Completed: 20260921 Latest Revision: 20260923 |
| Update Code: | 20260923 |
| PubMed Central ID: | PMC13592487 |
| DOI: | 10.1002/epi.70360 |
| PMID: | 42400436 |
| Βάση Δεδομένων: | MEDLINE |
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