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

T. Smol; F. Petit; A. Piton; B. Keren; D. Sanlaville; A. Afenjar; S. Baker; E. Bedoukian; E. Bhoj; D. Bonneau; E. Boudry-Labis; S. Bouquillon; O. Boute-Benejean; R. Caumes; N. Chatron; Cindy Colson; C. Coubes; C. Coutton; F. Devillard; A. Dieux-Coeslier; M. Doco-Fenzy; L.J. Ewans; L. Faivre; E. Fassi; M. Field; Clarisse Fournier; C. Francannet; D. Geneviève; I. Giurgea; A. Goldenberg; A. Green; A. Guerrot; D. Heron; B. Isidor; B. Keena; B. Krock; P. Kuentz; E. Lapi; N. Le Meur; G. Lesca; D. Li; I. Marey; C. Mignot; C. Nava; A. Nesbitt; G. Nicolas; C. Roche-Lestienne; T. Roscioli; V. Satre; A. Santani; M. Stefanova; S. Steinwall Larsen; P. Saugier-Veber; S. Picker-Minh; C. Thuillier; A. Verloes; G. Vieville; M. Wenzel; M. Willems; S. Whalen; Y. Zarate; A. Ziegler; S. Manouvrier-Hanu; V. Kalscheuer; B. Gérard; Jamal Ghoumid

doi:10.1007/s10048-018-0541-0

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

Journal article

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

T. Smol, F. Petit, A. Piton, B. Keren, D. Sanlaville, A. Afenjar, S. Baker, E. Bedoukian, E. Bhoj, D. Bonneau, …

neurogenetics, Vol.19(2), pp.93-103

05/2018

DOI: https://doi.org/10.1007/s10048-018-0541-0

PMID: 29511999

Abstract

MED13L

Cardiopathy

Intellectual disability

Mediator complex

Child

Child, Preschool

Female

Humans

Intellectual Disability

Male

Mediator Complex

Mutation, Missense

Phenotype

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.

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Title: MED13L-related intellectual disability: involvement of missense variants and delineation of the phenotype
Creators - without role: T. Smol - Hôpital Jeanne de Flandre
F. Petit - Hôpital Jeanne de Flandre
A. Piton - Laboratoire de Diagnostic Génétique [CHU Strasbourg]
B. Keren - Pitié-Salpêtrière Hospital
D. Sanlaville - Hospices Civils de Lyon
A. Afenjar - Assistance Publique – Hôpitaux de Paris
S. Baker - Children's Hospital of Philadelphia
E. Bedoukian - Children's Hospital of Philadelphia
E. Bhoj - Children's Hospital of Philadelphia
D. Bonneau - Centre Hospitalier Universitaire d'Angers
E. Boudry-Labis - Service de Génétique Médicale [Lille]
S. Bouquillon - Service de Génétique Médicale [Lille]
O. Boute-Benejean - Hôpital Jeanne de Flandre
R. Caumes - Institut de Biologie de Lille
N. Chatron - Hospices Civils de Lyon
Cindy Colson - Centre Hospitalier Universitaire de Lille
C. Coubes - Département de génétique médicale, maladies rares et médecine personnalisée [CHU Montpellier]
C. Coutton - Centre National de la Recherche Scientifique
F. Devillard - Laboratoire de Génétique Cellulaire
A. Dieux-Coeslier - Hôpital Jeanne de Flandre
M. Doco-Fenzy - Australian Defence Force Academy
L.J. Ewans - Australian Defence Force Academy
L. Faivre - Centre Hospitalier Universitaire Dijon Bourgogne
E. Fassi - Washington University in St. Louis
M. Field - Hunter Genetics
Clarisse Fournier - Laboratoire de Diagnostic Génétique [CHU Strasbourg]
C. Francannet - Centre Hospitalier Universitaire de Clermont-Ferrand
D. Geneviève - Département de génétique médicale, maladies rares et médecine personnalisée [CHU Montpellier]
I. Giurgea - Assistance Publique – Hôpitaux de Paris
A. Goldenberg - Biotherapy of Genetic Diseases, Inflammatory Disorders and Cancers
A. Green - Linköping University Hospital
A. Guerrot - Biotherapy of Genetic Diseases, Inflammatory Disorders and Cancers
D. Heron - Sorbonne Université
B. Isidor - Génétique Médicale & Génomique Fonctionelle
B. Keena - Children's Hospital of Philadelphia
B. Krock - Children's Hospital of Philadelphia
P. Kuentz - Centre de recherche Translationnelle en Médecine moléculaire
E. Lapi - Meyer Children's Hospital
N. Le Meur - Biotherapy of Genetic Diseases, Inflammatory Disorders and Cancers
G. Lesca - Hospices Civils de Lyon
D. Li - Children's Hospital of Philadelphia
I. Marey - Pitié-Salpêtrière Hospital
C. Mignot - Pitié-Salpêtrière Hospital
C. Nava - Sorbonne Université
A. Nesbitt - Children's Hospital of Philadelphia
G. Nicolas - Biotherapy of Genetic Diseases, Inflammatory Disorders and Cancers
C. Roche-Lestienne - Service de Génétique Médicale [Lille]
T. Roscioli - Australian Defence Force Academy
V. Satre - Laboratoire de Génétique Cellulaire
A. Santani - Children's Hospital of Philadelphia
M. Stefanova - Linköping University Hospital
S. Steinwall Larsen - Linköping University Hospital
P. Saugier-Veber - Biotherapy of Genetic Diseases, Inflammatory Disorders and Cancers
S. Picker-Minh - Charité - Universitätsmedizin Berlin
C. Thuillier - Centre Hospitalier Universitaire de Grenoble
A. Verloes - Hôpital Robert-Debré
G. Vieville - Laboratoire de Génétique Cellulaire
M. Wenzel - Children's Hospital of Philadelphia
M. Willems - Génétique Médicale & Génomique Fonctionelle
S. Whalen - Pitié-Salpêtrière Hospital
Y. Zarate - University of Arkansas for Medical Sciences
A. Ziegler - Centre Hospitalier Universitaire d'Angers
S. Manouvrier-Hanu - Centre Hospitalier Universitaire de Lille
V. Kalscheuer - Max Planck Institute for Molecular Genetics
B. Gérard - Laboratoire de Diagnostic Génétique [CHU Strasbourg]
Jamal Ghoumid - Hôpital Jeanne de Flandre
Publication Details: neurogenetics, Vol.19(2), pp.93-103
Identifiers: 9935622209311
Academic Unit: Cell souches plasticité cellul régénérat tissulaire immuno des maladies inflamm - IRMB
Language: English
Resource Type: Journal article
Local Fields: hal-02393664