Copy Number Variation and Epilepsy: State of the Art in the Era of High-Throughput Sequencing-A Multicenter Cohort Study.

Autor: Baer S; Department of Neuropediatrics, ERN EpiCare, French Centre de référence des Épilepsies Rares (CréER), Hôpitaux Universitaires de Strasbourg, Strasbourg, France; Institute for Genetics and Molecular and Cellular Biology (IGBMC), University of Strasbourg, CNRS UMR7104, INSERM U1258, Illkirch, France. Electronic address: sarah.baer@chru-strasbourg.fr., Schalk A; Laboratories of Genetic Diagnosis, Institut de Génétique Médicale d'Alsace (IGMA), Strasbourg University Hospitals Strasbourg France, Strasbourg, France., Miguet M; Department of Genetics, Emile Muller Hospital, Mulhouse, France., Schaefer É; Clinical Genetics Unit, Institut de Génétique Médicale d'Alsace (IGMA), Strasbourg, France., El Chehadeh S; Clinical Genetics Unit, Institut de Génétique Médicale d'Alsace (IGMA), Strasbourg, France., Ginglinger E; Department of Genetics, Emile Muller Hospital, Mulhouse, France., de Saint Martin A; Department of Neuropediatrics, ERN EpiCare, French Centre de référence des Épilepsies Rares (CréER), Hôpitaux Universitaires de Strasbourg, Strasbourg, France., Abi Wardé MT; Department of Neuropediatrics, ERN EpiCare, French Centre de référence des Épilepsies Rares (CréER), Hôpitaux Universitaires de Strasbourg, Strasbourg, France., Laugel V; Department of Neuropediatrics, ERN EpiCare, French Centre de référence des Épilepsies Rares (CréER), Hôpitaux Universitaires de Strasbourg, Strasbourg, France., de Feraudy Y; Department of Neuropediatrics, ERN EpiCare, French Centre de référence des Épilepsies Rares (CréER), Hôpitaux Universitaires de Strasbourg, Strasbourg, France., Gauer L; Epilepsy Unit 'Francis Rohmer,' ERN EpiCare, French Centre de référence des Épilepsies Rares (CréER), Neurology Department, Hôpitaux Universitaires de Strasbourg, Strasbourg, France., Hirsch E; Epilepsy Unit 'Francis Rohmer,' ERN EpiCare, French Centre de référence des Épilepsies Rares (CréER), Neurology Department, Hôpitaux Universitaires de Strasbourg, Strasbourg, France., Boulay C; Epilepsy Unit 'Francis Rohmer,' ERN EpiCare, French Centre de référence des Épilepsies Rares (CréER), Neurology Department, Hôpitaux Universitaires de Strasbourg, Strasbourg, France; Department of Pediatrics, Émile Muller Hospital, Mulhouse, France., Bansept C; Department of Pediatrics, Émile Muller Hospital, Mulhouse, France., Bolocan A; Department of Pediatrics, Émile Muller Hospital, Mulhouse, France., Kitadinis I; Department of Pediatrics, Émile Muller Hospital, Mulhouse, France., Gouronc A; Laboratories of Genetic Diagnosis, Institut de Génétique Médicale d'Alsace (IGMA), Strasbourg University Hospitals Strasbourg France, Strasbourg, France., Gérard B; Laboratories of Genetic Diagnosis, Institut de Génétique Médicale d'Alsace (IGMA), Strasbourg University Hospitals Strasbourg France, Strasbourg, France., Piton A; Institute for Genetics and Molecular and Cellular Biology (IGBMC), University of Strasbourg, CNRS UMR7104, INSERM U1258, Illkirch, France; Laboratories of Genetic Diagnosis, Institut de Génétique Médicale d'Alsace (IGMA), Strasbourg University Hospitals Strasbourg France, Strasbourg, France., Scheidecker S; Laboratories of Genetic Diagnosis, Institut de Génétique Médicale d'Alsace (IGMA), Strasbourg University Hospitals Strasbourg France, Strasbourg, France.
Jazyk: angličtina
Zdroj: Pediatric neurology [Pediatr Neurol] 2024 Oct; Vol. 159, pp. 16-25. Date of Electronic Publication: 2024 Jul 15.
DOI: 10.1016/j.pediatrneurol.2024.07.007
Abstrakt: Background: Genetic epilepsy diagnosis is increasing due to technological advancements. Although the use of molecular diagnosis is increasing, chromosomal microarray analysis (CMA) remains an important diagnostic tool for many patients. We aim to explore the role and indications of CMA in epilepsy, given the current genomic advances.
Methods: We obtained data from 378 epileptic described patients, who underwent CMA between 2015 and 2021. Different types of syndromic or nonsyndromic epilepsy were represented.
Results: After excluding patients who were undertreated or had missing data, we included 250 patients with treated epilepsy and relevant clinical information. These patients mostly had focal epilepsy or developmental and epileptic encephalopathy, with a median start age of 2 years. Ninety percent of the patients had intellectual disability, more than two thirds had normal head size, and 60% had an abnormal magnetic resonance imaging. We also included 10 patients with epilepsy without comorbidities. In our cohort, we identified 35 pathogenic copy number variations (CNVs) explaining epilepsy with nine recurrent CNVs enriched in patients with epilepsy, 12 CNVs related to neurodevelopmental disorder phenotype with possible epilepsy, five CNVs including a gene already known in epilepsy, and nine CNVs based on size combined with de novo occurrence. The diagnosis rate in our study reached 14% (35 of 250) with first-line CMA, as previously reported. Although targeted gene panel sequencing could potentially diagnose some of the reported epilepsy CNVs (34% [12 of 35]).
Conclusions: CMA remains a viable option as the first-line genetic test in cases where other genetic tests are not available and as a second-line diagnostic technique if gene panel or exome sequencing yields negative results.
Competing Interests: Declaration of competing interest None of the authors have any conflicts of interest related to this study to declare.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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