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Clin Genet. 2018 Mar;93(3):567-576. doi: 10.1111/cge.13102. Epub 2017 Oct 4.

Using medical exome sequencing to identify the causes of neurodevelopmental disorders: Experience of 2 clinical units and 216 patients.

Author information

1
Service de Génétique Médicale, CLAD Ouest CHU Hôpital Sud, Rennes, France.
2
Laboratoire de Génétique moléculaire et Génomique, CHU Pontchaillou, Rennes, France.
3
Département de Génétique, AP-HP, Hôpital 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 Hôpital de la Pitié-Salpêtrière, Paris, France.
8
APHP, GHUEP, Hôpital Armand Trousseau, Centre de Référence 'Malformations et maladies congénitales du cervelet', Paris, France.
9
Département de Génétique, APHP, GHUEP, Hôpital Armand-Trousseau, Paris, France.
10
AP-HP, Service de Neuropédiatrie, Hôpital Armand Trousseau, Paris, France.
11
AP-HP, Hôpital Armand Trousseau, Centre de Référence Neurogénétique de l'Enfant à l'adulte, Paris, France.
12
AP-HP, Service de Pédiatrie, Hôpital 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.

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.

KEYWORDS:

autism; intellectual disability; medical exome; molecular strategy

PMID:
28708303
DOI:
10.1111/cge.13102
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