title: A transcription factor involved in skeletal muscle gene expression is deleted in patients with Williams syndrome.
abstract: Williams-Beuren syndrome (WS) is a developmental disorder caused by a hemizygous microdeletion of approximately 1.4MB 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.
authors.affiliation: University Department of Medical Genetics, St Mary's Hospital, Manchester, UK. M.Tassabehji@man.ac.uk
authors.forename: M
authors.initials: M
authors.lastname: Tassabehji
authors.forename: M
authors.initials: M
authors.lastname: Carette
authors.forename: C
authors.initials: C
authors.lastname: Wilmot
authors.forename: D
authors.initials: D
authors.lastname: Donnai
authors.forename: A P
authors.initials: AP
authors.lastname: Read
authors.forename: K
authors.initials: K
authors.lastname: Metcalfe
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D015152:Blotting, Northern; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D017353:Gene Deletion; D015870:Gene Expression; D020869:Gene Expression Profiling; D015723:Gene Library; D018257:Helix-Loop-Helix Motifs; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008969:Molecular Sequence Data; D009124:Muscle Proteins; D018482:Muscle, Skeletal / Q000378:metabolism*; D009687:Nuclear Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D018980:Williams Syndrome / Q000235:genetics* / Q000378:metabolism
chemical_list: D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C405493:GTF2IRD1 protein, human; D009124:Muscle Proteins; D009687:Nuclear Proteins; D015534:Trans-Activators; D014157:Transcription Factors