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GTF2IRD1 in craniofacial development of humans and mice

journal contribution
posted on 2023-06-08, 05:09 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 Donnai
Craniofacial 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

History

Publication status

  • Published

Journal

Science

ISSN

0036-8075

Publisher

American Association for the Advancement of Science

Issue

5751

Volume

310

Page range

1184-1187

Department affiliated with

  • Neuroscience Publications

Notes

On this collaboration, my contribution was to generate the transgenic mice, carry out some of the analyses, as well as contributing towards to the experimental design, in preparing the manuscript with the lead author and responding to review.

Full text available

  • No

Peer reviewed?

  • Yes

Legacy Posted Date

2013-02-12

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