Research: Craniofacial development genes

18 November 2005

Deletion of the transcription factor gene GTF2IRD1 has been identified as a cause of some of the craniofacial defects seen in Williams–Beuren syndrome, a rare congenital craniofacial and neurological disorder that affects about 1 in 20 000 people.

The syndrome is characterised by a distinctive facial appearance, short stature, heart and blood vessel problems, an overly friendly personality, and numerical and spatial difficulties. Severe cases are caused by a deletion in one chromosome 7 homologue that removes 28 genes, but some people have smaller deletions and only some of the disorder’s features. Dr May Tassabehji (a Wellcome Trust Senior Research Fellow at the University of Manchester) and colleagues have been studying the latter individuals to pinpoint which deleted genes are associated with which features of the disorder.

One key individual they identified with a smaller deletion had milder mental retardation and cognitive deficits, and less severe facial changes (measured using 3D face-imaging technology). Dr Tassabehji found that the transcription factor gene GTF2IRD1 was disrupted, and went on to show that mice with deletions of both copies of the equivalent Gtf2ird1 gene had defects reminiscent of the human condition: they were small and had craniofacial abnormalities including short snouts and fullness around the eyes, and some had twisted snouts with misaligned jaws.

People with severe Williams–Beuren syndrome have larger deletions and have lost additional genes – in particular GTF2I, a transcription factor related to GTF2IRD1. The researchers suggest that losing GTF2IRD1 has mild effects, but losing both GTF2IRD1 and GTF2I leads to most of the pathologies associated with the full syndrome.

External links

• Tassabehji M et al. GTF2IRD1 in craniofacial development of humans and mice. Science 2005;310(5751):1184–7.