De novo TBR1 variants cause a neurocognitive phenotype with ID and autistic traits: report of 25 new individuals and review of the literature - Maladies génétiques d'expression pédiatrique Accéder directement au contenu
Article Dans Une Revue European Journal of Human Genetics Année : 2020

De novo TBR1 variants cause a neurocognitive phenotype with ID and autistic traits: report of 25 new individuals and review of the literature

Sophie Nambot (1, 2, 3) , Laurence Faivre (1, 2, 3) , Ghayda Mirzaa (4, 5) , Julien Thevenon (1, 2, 3, 6) , Ange-Line Bruel (1, 2, 6) , Anne-Laure Mosca-Boidron (1, 2, 6) , Alice Masurel-Paulet (1, 3) , Alice Goldenberg (7) , Nathalie Le Meur (7) , Aude Charollais (8) , Cyril Mignot (9) , Florence Petit (10) , Massimiliano Rossi (11, 12, 13) , Julia Metreau (14) , Valérie Layet (15) , Daniel Amram (16) , Odile Boute-Bénéjean (10) , Elizabeth Bhoj (17, 18) , Margot Cousin (19) , Teresa Kruisselbrink (19) , Brendan Lanpher (19) , Eric Klee (19) , Elise Fiala (20) , Dorothy Grange (21) , Wendy Meschino , Susan Hiatt (22) , Gregory Cooper (22) , Hilde Olivié (23) , Wendy Smith (24) , Meghan Dumas (24) , Anna Lehman (25) , Cara Inglese (25) , Mathilde Nizon (26) , Renzo Guerrini (27, 28) , Annalisa Vetro (27, 28) , Eitan Kaplan (5) , Dolores Miramar , Julien van Gils (29) , Patricia Fergelot (29) , Olaf Bodamer (30) , Johanna Herkert (31) , Sander Pajusalu (32) , Katrin Õunap (32) , James Filiano (33) , Thomas Smol (34) , Amélie Piton (35) , Bénédicte Gérard (35) , Sandra Chantot-Bastaraud (36, 9) , Thierry Bienvenu (37) , Dong Li (19) , Jane Juusola (38) , Koen Devriendt (23) , Frederic Bilan (39) , Charlotte Poé (40) , Martin Chevarin (40) , Thibaud Jouan (40) , Emilie Tisserant (40) , Jean-Baptiste Rivière (40, 3, 6) , Frédéric Tran Mau-Them (40, 6) , Christophe Philippe (40, 6) , Yannis Duffourd (40, 6) , William Dobyns (4) , Robert Hevner (4) , Christel Thauvin-Robinet (1, 40, 3, 6)
1 Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon)
2 LNC - Lipides - Nutrition - Cancer [Dijon - U1231]
3 FHU TRANSLAD (CHU de Dijon)
4 Center for Integrative Brain Research [Seattle, WA, USA]
5 Department of Pediatrics [Seattle]
6 UF6254 - Unité fonctionnelle d' Innovation en Diagnostic Génomique des Maladies Rares (CHU Dijon)
7 Service de Génétique [CHU Rouen]
8 Service de pédiatrie médicale et médecine de l'adolescent [Rouen]
9 CHU Trousseau [APHP]
10 Clinique de Génétique médicale Guy Fontaine [CHRU LIlle]
11 Centre de pathologie de l'Est - Service de Génétique [CHU Lyon]
12 CRNL - Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center
13 GENDEV - Genetics of Neurodevelopment
14 Service de Neurologie Pédiatrique [CHU Bicêtre]
15 Département de génétique (groupe hospitalier le Havre)
16 CHIC - Centre Hospitalier Intercommunal de Créteil
17 Division of Genetics - Department of Pediatrics [Philadelphia, PA, USA]
18 The Center for Applied Genomics [Philadelphia, PA, USA]
19 Mayo Clinic [Rochester]
20 Division of Genetics and Genomic Medicine - Department of Pediatrics [Saint Louis, MO, USA]
21 Department of Genetics [Saint-Louis]
22 HudsonAlpha Institute for Biotechnology [Huntsville, AL]
23 University Hospitals Leuven [Leuven]
24 Maine Medical Center
25 University of British Columbia [Vancouver]
26 Service de génétique médicale - Unité de génétique clinique [Nantes]
27 Meyer Children's Hospital [Florence, Italie]
28 UniFI - Università degli Studi di Firenze = University of Florence
29 CHU Bordeaux
30 Department of Genetics [Boston]
31 UMCG - University Medical Center Groningen [Groningen]
32 University of Tartu
33 DHMC - Dartmouth Hitchcock Medical Center
34 Service de Génétique Médicale [Lille]
35 Laboratoire de Diagnostic Génétique [CHU Strasbourg]
36 U933 - Maladies génétiques d'expression pédiatrique
37 Service de Génétique et Biologie Moléculaires [CHU Cochin]
38 GeneDx [Gaithersburg, MD, USA]
39 Service Génétique Médicale [CHU Poitiers]
40 LNC - Lipides - Nutrition - Cancer [Dijon - U1231]
Margot Cousin
Wendy Meschino
  • Fonction : Auteur
Wendy Smith
  • Fonction : Auteur
Dolores Miramar
  • Fonction : Auteur
Julien van Gils
  • Fonction : Auteur
Patricia Fergelot
  • Fonction : Auteur
Sander Pajusalu
Katrin Õunap
Thomas Smol
Dong Li
  • Fonction : Auteur

Résumé

TBR1, a T-box transcription factor expressed in the cerebral cortex, regulates the expression of several candidate genes for autism spectrum disorders (ASD). Although TBR1 has been reported as a high-confidence risk gene for ASD and intellectual disability (ID) in functional and clinical reports since 2011, TBR1 has only recently been recorded as a human disease gene in the OMIM database. Currently, the neurodevelopmental disorders and structural brain anomalies associated with TBR1 variants are not well characterized. Through international data sharing, we collected data from 25 unreported individuals and compared them with data from the literature. We evaluated structural brain anomalies in seven individuals by analysis of MRI images, and compared these with anomalies observed in TBR1 mutant mice. The phenotype included ID in all individuals, associated to autistic traits in 76% of them. No recognizable facial phenotype could be identified. MRI analysis revealed a reduction of the anterior commissure and suggested new features including dysplastic hippocampus and subtle neocortical dysgenesis. This report supports the role of TBR1 in ID associated with autistic traits and suggests new structural brain malformations in humans. We hope this work will help geneticists to interpret TBR1 variants and diagnose ASD probands.
Fichier sous embargo
Fichier sous embargo
Date de visibilité indéterminée

Dates et versions

inserm-03846561 , version 1 (10-11-2022)

Identifiants

Citer

Sophie Nambot, Laurence Faivre, Ghayda Mirzaa, Julien Thevenon, Ange-Line Bruel, et al.. De novo TBR1 variants cause a neurocognitive phenotype with ID and autistic traits: report of 25 new individuals and review of the literature. European Journal of Human Genetics, 2020, 28 (6), pp.770-782. ⟨10.1038/s41431-020-0571-6⟩. ⟨inserm-03846561⟩
68 Consultations
1 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More