MED13L-related intellectual disability: involvement of missense variants and delineation of the phenotype - Université de Bourgogne Accéder directement au contenu
Article Dans Une Revue neurogenetics Année : 2018

MED13L-related intellectual disability: involvement of missense variants and delineation of the phenotype

1 Service de Génétique Médicale [Lille]
2 RADEME - Maladies RAres du DEveloppement embryonnaire et du MEtabolisme : du Phénotype au Génotype et à la Fonction - ULR 7364
3 Pôle de Biologie Pathologie Génétique [CHU Lille]
4 Laboratoire de Diagnostic Génétique [CHU Strasbourg]
5 CHU Pitié-Salpêtrière [AP-HP]
6 Laboratoire de Cytogénétique Constitutionnelle [Hospices civils de Lyon]
7 CHU Trousseau [APHP]
8 CHOP - Children’s Hospital of Philadelphia
9 Service de génétique [Angers]
10 MITOVASC - MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale
11 Département de génétique médicale, maladies rares et médecine personnalisée [CHRU Montpellier]
12 IAB - Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble)
13 Laboratoire de Génétique Chromosomique [CHU de Grenoble]
14 UNSW - University of New South Wales [Canberra Campus]
15 Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon)
16 LNC - Lipides - Nutrition - Cancer [Dijon - U1231]
17 Washington University School of Medicine in St. Louis
18 Service de Génétique Médicale [CHU Clermont-Ferrand]
19 U933 - Maladies génétiques d'expression pédiatrique
20 GMFC - Génétique du cancer et des maladies neuropsychiatriques
21 Linköping university hospital
22 Service de génétique médicale - Unité de génétique clinique [Nantes]
23 Azienda Ospedaliero Universitaria A. Meyer [Firenze, Italy]
24 Charité - UniversitätsMedizin = Charité - University Hospital [Berlin]
25 CHUGA - Centre Hospitalier Universitaire [CHU Grenoble]
26 Unité fonctionnelle de génétique clinique
27 Département de génétique [Robert Debré]
28 Service de génétique médicale [Montpellier]
29 UAMS - University of Arkansas for Medical Sciences
30 MPIMG - Max Planck Institute for Molecular Genetics
A. Afenjar
  • Fonction : Auteur
S. Baker
M. Field
  • Fonction : Auteur

Résumé

Molecular anomalies in MED13L, leading to haploinsufficiency, have been reported in patients with moderate to severe intellectual disability (ID) and distinct facial features, with or without congenital heart defects. Phenotype of the patients was referred to "MED13L haploinsufficiency syndrome." Missense variants in MED13L were already previously described to cause the MED13L-related syndrome, but only in a limited number of patients. Here we report 36 patients with MED13L molecular anomaly, recruited through an international collaboration between centers of expertise for developmental anomalies. All patients presented with intellectual disability and severe language impairment. Hypotonia, ataxia, and recognizable facial gestalt were frequent findings, but not congenital heart defects. We identified seven de novo missense variations, in addition to protein-truncating variants and intragenic deletions. Missense variants clustered in two mutation hot-spots, i.e., exons 15-17 and 25-31. We found that patients carrying missense mutations had more frequently epilepsy and showed a more severe phenotype. This study ascertains missense variations in MED13L as a cause for MED13L-related intellectual disability and improves the clinical delineation of the condition.

Dates et versions

hal-02393664 , version 1 (04-12-2019)

Identifiants

Citer

T. Smol, F. Petit, A. Piton, B. Keren, D. Sanlaville, et al.. MED13L-related intellectual disability: involvement of missense variants and delineation of the phenotype. neurogenetics, 2018, 19 (2), pp.93-103. ⟨10.1007/s10048-018-0541-0⟩. ⟨hal-02393664⟩
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