A transcription factor involved in skeletal muscle gene expression is deleted in patients with Williams syndrome

Mayada Tassabehji, Martin Carette, Carrie Wilmot, Dian Donnai, Andrew P. Read, Kay Metcalfe

Research output: Contribution to journalArticlepeer-review

32 Scopus citations


Williams-Beuren syndrome (WS) is a developmental disorder caused by a hemizygous microdeletion of approximately 1.4 MB at chromosomal location 7q11.23. The transcription map of the WS critical region is not yet complete. We have isolated and characterised a 3.4 kb gene, GTF3, which occupies about 140 kb of the deleted region. Northern blot analysis showed that the gene is expressed in skeletal muscle and heart, and RT-PCR analysis showed expression in a range of adult tissues with stronger expression in foetal tissues. Part of the conceptual GTF3 protein sequence is almost identical to a recently reported slow muscle-fibre enhancer binding protein MusTRD1, and shows significant homology to the 90 amino-acid putative helix-loop-helix repeat (HLH) domains of the transcription factor TFII-I (encoded for by the gene GTF2I). These genes may be members of a new family of transcription factors containing this HLH-like repeated motif. Both GTF3 and GTF2I map within the WS deleted region, with GTF2I being positioned distal to GTF3. GTF3 is deleted in patients with classic WS, but not in patients we have studied with partial deletions of the WS critical region who have only supravalvular aortic stenosis. A feature of WS is abnormal muscle fatiguability, and we suggest that haploinsufficiency of the GTF3 gene may be the cause of this.

Original languageEnglish (US)
Pages (from-to)737-747
Number of pages11
JournalEuropean Journal of Human Genetics
Issue number7
StatePublished - Oct 1999

Bibliographical note

Funding Information:
We thank Mr William Fergusson for contributing to the cell culture work and Mr Steven Smith and Mr John Nelson (UK Williams Syndrome Foundation committee) for their helpful comments. Also the patients involved in the study are thanked for their co-operation. MT was supported by the Wellcome Trust, (grant no 045998). MJC was supported by Action Research/SPARKS (grant S/P/3073). KM was supported by Birth Defects.


  • Fatigue-resistant slow fibres
  • GTF3
  • HLH-like repeated motif
  • Skeletal muscle
  • Skeletal muscle gene expression
  • Transcription factor
  • Williams-Beuren syndrome (WS)


Dive into the research topics of 'A transcription factor involved in skeletal muscle gene expression is deleted in patients with Williams syndrome'. Together they form a unique fingerprint.

Cite this