De novo TBR1 variants cause a neurocognitive phenotype with ID and autistic traits: report of 25 new individuals and review of the literature.
Eur J Hum Genet
; 28(6): 770-782, 2020 06.
Article
in En
| MEDLINE
| ID: mdl-32005960
ABSTRACT
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Phenotype
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Autistic Disorder
/
Craniofacial Abnormalities
/
T-Box Domain Proteins
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Intellectual Disability
Type of study:
Prognostic_studies
Limits:
Adolescent
/
Adult
/
Animals
/
Child
/
Child, preschool
/
Female
/
Humans
/
Male
Language:
En
Journal:
Eur J Hum Genet
Journal subject:
GENETICA MEDICA
Year:
2020
Document type:
Article
Affiliation country:
France