GTF2IRD1 in craniofacial development of humans and mice

Science. 2005 Nov 18;310(5751):1184-7. doi: 10.1126/science.1116142. Epub 2005 Nov 3.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Animals
  • Cell Line
  • Child
  • Child, Preschool
  • Chromosomes, Human, Pair 7
  • Craniofacial Abnormalities / genetics*
  • Face / embryology*
  • Female
  • Gene Deletion
  • Goosecoid Protein / genetics
  • Goosecoid Protein / 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*


  • GTF2I protein, human
  • GTF2IRD1 protein, human
  • Goosecoid Protein
  • Gsc protein, mouse
  • Gtf2i protein, mouse
  • Gtf2ird1 protein, mouse
  • Muscle Proteins
  • Nuclear Proteins
  • Trans-Activators
  • Transcription Factors, TFII