Publication Date:
2005-11-19
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tassabehji, May -- Hammond, Peter -- Karmiloff-Smith, Annette -- Thompson, Pamela -- Thorgeirsson, Snorri S -- Durkin, Marian E -- Popescu, Nicholas C -- Hutton, Timothy -- Metcalfe, Kay -- Rucka, Agnes -- Stewart, Helen -- Read, Andrew P -- Maconochie, Mark -- Donnai, Dian -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2005 Nov 18;310(5751):1184-7. Epub 2005 Nov 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Academic Unit of Medical Genetics, University of Manchester, St. Mary's Hospital, Manchester M13 9PL, UK. m.tassabehji@manchester.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16293761" target="_blank"〉PubMed〈/a〉
Keywords:
Adolescent
;
Adult
;
Animals
;
Cell Line
;
Child
;
Child, Preschool
;
Chromosomes, Human, Pair 7
;
Craniofacial Abnormalities/*genetics
;
Face/*embryology
;
Female
;
Gene Deletion
;
Goosecoid Protein/genetics/physiology
;
Homozygote
;
Humans
;
Infant
;
Infant, Newborn
;
Male
;
Mice
;
Mice, Inbred C57BL
;
Mice, Inbred CBA
;
Mice, Transgenic
;
Muscle Proteins/*physiology
;
Nuclear Proteins/*physiology
;
Skull/*embryology
;
Trans-Activators/*physiology
;
Transcription Factors, TFII/physiology
;
Williams Syndrome/*genetics
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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