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GTF2IRD1 in craniofacial development of humans and mice
journal contribution
posted on 2023-06-07, 21:49 authored by May Tassabehji, Peter Hammond, Annette Karmiloff-Smith, Pamela Thompson, Snorri S Thorgeirsson, Marian E Durkin, Nicholas C Popescu, Timothy Hutton, Kay Metcalfe, Agnes Rucka, Helen Stewart, Andrew P Read, Mark Maconochie, Dian DonnaiCraniofacial abnormalities account for about one-third of all human congenital defects, but our understanding of the genetic mechanisms governing craniofacial development is incomplete. We show that GTF2IRD1 is a genetic determinant of mammalian craniofacial and cognitive development, and we implicate another member of the TFII-I transcription factor family, GTF2I, in both aspects. Gtf2ird1-null mice exhibit phenotypic abnormalities reminiscent of the human microdeletion disorder Williams-Beuren syndrome (WBS); craniofacial imaging reveals abnormalities in both skull and jaws that may arise through misregulation of goosecoid, a downstream target of Gtf2ird1. In humans, a rare WBS individual with an atypical deletion, including GTF2IRD1, shows facial dysmorphism and cognitive deficits that differ from those of classic WBS cases. We propose a mechanism of cumulative dosage effects of duplicated and diverged genes applicable to other human chromosomal disorders.
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Publication status
- Published
Journal
ScienceISSN
0036-8075External DOI
Issue
5751Volume
310Page range
1184-1187Pages
4.0Department affiliated with
- Neuroscience Publications
Full text available
- No
Peer reviewed?
- Yes
Legacy Posted Date
2012-02-06Usage metrics
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