title: Mutations in TWIST, a basic helix-loop-helix transcription factor, in Saethre-Chotzen syndrome.
abstract: Saethre-Chotzen syndrome is one of the most common autosomal dominant disorders of craniosynostosis in humans and is characterized by craniofacial and limb anomalies. The locus for Saethre-Chotzen syndrome maps to chromosome 7p21-p22. We have evaluated TWIST, a basic helix-loop-helix transcription factor, as a candidate gene for this condition because its expression pattern and mutant phenotypes in Drosophila and mouse are consistent with the Saethre-Chotzen phenotype. We mapped TWIST to human chromosome 7p21-p22 and mutational analysis reveals nonsense, missense, insertion and deletion mutations in patients. These mutations occur within the basic DNA binding, helix I and loop domains, or result in premature termination of the protein. Studies in Drosophila indicate that twist may affect the transcription of fibroblast growth factor receptors (FGFRs), another gene family implicated in human craniosynostosis. The emerging cascade of molecular components involved in craniofacial and limb development now includes TWIST, which may function as an upstream regulator of FGFRs.
authors.affiliation: Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, Maryland 21287-3914, USA.
authors.forename: T D
authors.initials: TD
authors.lastname: Howard
authors.forename: W A
authors.initials: WA
authors.lastname: Paznekas
authors.forename: E D
authors.initials: ED
authors.lastname: Green
authors.forename: L C
authors.initials: LC
authors.lastname: Chiang
authors.forename: N
authors.initials: N
authors.lastname: Ma
authors.forename: R I
authors.initials: RI
authors.lastname: Ortiz de Luna
authors.forename: C
authors.initials: C
authors.lastname: Garcia Delgado
authors.forename: M
authors.initials: M
authors.lastname: Gonzalez-Ramos
authors.forename: A D
authors.initials: AD
authors.lastname: Kline
authors.forename: E W
authors.initials: EW
authors.lastname: Jabs
mesh_terms: D000168:Acrocephalosyndactylia / Q000235:genetics*; D002874:Chromosome Mapping; D018244:Chromosomes, Artificial, Yeast; D002897:Chromosomes, Human, Pair 7; D004252:DNA Mutational Analysis; D005260:Female; D018257:Helix-Loop-Helix Motifs; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins; D010375:Pedigree; D014157:Transcription Factors / Q000235:genetics*; D051879:Twist-Related Protein 1
chemical_list: D009687:Nuclear Proteins; C103173:TWIST1 protein, human; D014157:Transcription Factors; D051879:Twist-Related Protein 1