GTF2IRD1 in Craniofacial Development of Humans and Mice
- 18 November 2005
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 310 (5751), 1184-1187
- https://doi.org/10.1126/science.1116142
Abstract
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.Keywords
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