De novo variants in TCF7L2 are associated with a syndromic neurodevelopmental disorder
Publication year
2021Author(s)
Source
American Journal of Medical Genetics. Part A, 185, 8, (2021), pp. 2384-2390ISSN
Publication type
Article / Letter to editor
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Organization
Human Genetics
Journal title
American Journal of Medical Genetics. Part A
Volume
vol. 185
Issue
iss. 8
Page start
p. 2384
Page end
p. 2390
Subject
Radboudumc 14: Tumours of the digestive tract RIMLS: Radboud Institute for Molecular Life Sciences; Radboudumc 7: Neurodevelopmental disorders DCMN: Donders Center for Medical Neuroscience; Human Genetics - Radboud University Medical CenterAbstract
TCF7L2 encodes transcription factor 7-like 2 (OMIM 602228), a key mediator of the evolutionary conserved canonical Wnt signaling pathway. Although several large-scale sequencing studies have implicated TCF7L2 in intellectual disability and autism, both the genetic mechanism and clinical phenotype have remained incompletely characterized. We present here a comprehensive genetic and phenotypic description of 11 individuals who have been identified to carry de novo variants in TCF7L2, both truncating and missense. Missense variation is clustered in or near a high mobility group box domain, involving this region in these variants' pathogenicity. All affected individuals present with developmental delays in childhood, but most ultimately achieved normal intelligence or had only mild intellectual disability. Myopia was present in approximately half of the individuals, and some individuals also possessed dysmorphic craniofacial features, orthopedic abnormalities, or neuropsychiatric comorbidities including autism and attention-deficit/hyperactivity disorder (ADHD). We thus present an initial clinical and genotypic spectrum associated with variation in TCF7L2, which will be important in informing both medical management and future research.
This item appears in the following Collection(s)
- Academic publications [246425]
- Faculty of Medical Sciences [93307]
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