Using medical exome sequencing to identify the causes of neurodevelopmental disorders: Experience of 2 clinical units and 216 patients |
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| Authors: | E. Chérot B. Keren C. Dubourg W. Carré M. Fradin A. Lavillaureix A. Afenjar L. Burglen S. Whalen P. Charles I. Marey S. Heide A. Jacquette D. Heron D. Doummar D. Rodriguez T. Billette de Villemeur M.‐L. Moutard A. Guët J. Xavier D. Périsse D. Cohen F. Demurger C. Quélin C. Depienne S. Odent C. Nava V. David L. Pasquier C. Mignot |
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| Affiliation: | 1. Service de Génétique Médicale, CLAD Ouest CHU H?pital Sud, Rennes, France;2. Laboratoire de Génétique moléculaire et Génomique, CHU Pontchaillou, Rennes, France;3. Département de Génétique, AP‐HP, H?pital de la Pitié‐Salpêtrière, Paris, France;4. Groupe de Recherche Clinique (GRC) "déficience intellectuelle et autisme", UPMC, Paris, France;5. Groupe de Recherche Clinique (GRC) "ConCer‐LD", UPMC, Paris, France;6. CNRS UMR 6290 (IGDR), Université de Rennes 1, Rennes, France;7. Centre de Référence Déficiences Intellectuelles de Causes Rares H?pital de la Pitié‐Salpêtrière, Paris, France;8. APHP, GHUEP, H?pital Armand Trousseau, Centre de Référence 'Malformations et maladies congénitales du cervelet', Paris, France;9. Département de Génétique, APHP, GHUEP, H?pital Armand‐Trousseau, Paris, France;10. AP‐HP, Service de Neuropédiatrie, H?pital Armand Trousseau, Paris, France;11. AP‐HP, H?pital Armand Trousseau, Centre de Référence Neurogénétique de l'Enfant à l'adulte, Paris, France;12. AP‐HP, Service de Pédiatrie, H?pital Louis Mourier, Colombes, France;13. AP‐HP, Department of Child and Adolescent Psychiatry, Groupe Hospitalier Pitié‐Salpêtrière et University Pierre and Marie Curie, Paris, France;14. Sorbonne Universités, UPMC, CNRS UMR 7222, Institut des Systèmes Intelligents et Robotiques, Paris, France;15. INSERM U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France;16. INSERM CIC pédiatrique 1414, CHU Pontchaillou, Rennes, France |
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| Abstract: | Although whole‐exome sequencing (WES) is the gold standard for the diagnosis of neurodevelopmental disorders (NDDs), it remains expensive for some genetic centers. Commercialized panels comprising all OMIM‐referenced genes called “medical exome” (ME) constitute an alternative strategy to WES, but its efficiency is poorly known. In this study, we report the experience of 2 clinical genetic centers using ME for diagnosis of NDDs. We recruited 216 consecutive index patients with NDDs in 2 French genetic centers, corresponded to the daily practice of the units and included non‐syndromic intellectual disability (NSID, n = 33), syndromic ID (NSID = 122), pediatric neurodegenerative disorders (n = 7) and autism spectrum disorder (ASD, n = 54). We sequenced samples from probands and their parents (when available) with the Illumina TruSight One sequencing kit. We found pathogenic or likely pathogenic variants in 56 index patients, for a global diagnostic yield of 25.9%. The diagnosis yield was higher in patients with ID as the main diagnosis (32%) than in patients with ASD (3.7%). Our results suggest that the use of ME is a valuable strategy for patients with ID when WES cannot be used as a routine diagnosis tool. |
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| Keywords: | autism intellectual disability medical exome molecular strategy |
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