De novo TBR1 variants cause a neurocognitive phenotype with ID and autistic traits: report of 25 new individuals and review of the literature.
Adolescent
Adult
Animals
Autistic Disorder
/ genetics
Child
Child, Preschool
Cognition
Craniofacial Abnormalities
/ genetics
Female
Hippocampus
/ diagnostic imaging
Humans
Intellectual Disability
/ genetics
Male
Mice
Mutation
Neocortex
/ diagnostic imaging
Phenotype
Syndrome
T-Box Domain Proteins
/ genetics
Journal
European journal of human genetics : EJHG
ISSN: 1476-5438
Titre abrégé: Eur J Hum Genet
Pays: England
ID NLM: 9302235
Informations de publication
Date de publication:
06 2020
06 2020
Historique:
received:
24
01
2019
accepted:
24
12
2019
revised:
26
11
2019
pubmed:
2
2
2020
medline:
28
5
2021
entrez:
2
2
2020
Statut:
ppublish
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.
Identifiants
pubmed: 32005960
doi: 10.1038/s41431-020-0571-6
pii: 10.1038/s41431-020-0571-6
pmc: PMC7253452
doi:
Substances chimiques
T-Box Domain Proteins
0
TBR1 protein, human
0
Types de publication
Case Reports
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
770-782Subventions
Organisme : NHGRI NIH HHS
ID : U01 HG007301
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS092339
Pays : United States
Organisme : NINDS NIH HHS
ID : K08 NS092898
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS085081
Pays : United States
Organisme : NHGRI NIH HHS
ID : UM1 HG007301
Pays : United States
Organisme : Canadian Institute of Health Research
Pays : International
Investigateurs
Shelin Adam
(S)
Christèle du Souich
(C)
Alison M Elliott
(AM)
Anna Lehman
(A)
Jill Mwenifumbo
(J)
Tanya N Nelson
(TN)
Clara van Karnebeek
(C)
Jan M Friedman
(JM)
Commentaires et corrections
Type : CommentIn
Type : CommentIn
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