title: Mutations of the TWIST gene in the Saethre-Chotzen syndrome.
abstract: Saethre-Chotzen syndrome (acrocephalo-syndactyly type III, ACS III) is an autosomal dominant craniosynostosis with brachydactyly, soft tissue syndactyly and facial dysmorphism including ptosis, facial asymmetry and prominent ear crura. ACS III has been mapped to chromosome 7p21-22. Of interest, TWIST, the human counterpart of the murine Twist gene, has been localized on chromosome 7p21 as well. The Twist gene product is a transcription factor containing a basic helix-loop-helix (b-HLH) domain, required in head mesenchyme for cranial neural tube morphogenesis in mice. The co-localisation of ACS III and TWIST prompted us to screen ACS III patients for TWIST gene mutations especially as mice heterozygous for Twist null mutations displayed skull defects and duplication of hind leg digits. Here, we report 21-bp insertions and nonsense mutations of the TWIST gene (S127X, E130X) in seven ACS III probands and describe impairment of head mesenchyme induction by TWIST as a novel pathophysiological mechanism in human craniosynostoses.
authors.affiliation: Unité Recherches sur les Handicaps Génétiques de l'Enfant INSERM U-393, Institut Necker, Paris, France.
authors.forename: V
authors.initials: V
authors.lastname: el Ghouzzi
authors.forename: M
authors.initials: M
authors.lastname: Le Merrer
authors.forename: F
authors.initials: F
authors.lastname: Perrin-Schmitt
authors.forename: E
authors.initials: E
authors.lastname: Lajeunie
authors.forename: P
authors.initials: P
authors.lastname: Benit
authors.forename: D
authors.initials: D
authors.lastname: Renier
authors.forename: P
authors.initials: P
authors.lastname: Bourgeois
authors.forename: A L
authors.initials: AL
authors.lastname: Bolcato-Bellemin
authors.forename: A
authors.initials: A
authors.lastname: Munnich
authors.forename: J
authors.initials: J
authors.lastname: Bonaventure
mesh_terms: D000168:Acrocephalosyndactylia / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002897:Chromosomes, Human, Pair 7; D004247:DNA; D005260:Female; D018257:Helix-Loop-Helix Motifs; D006801:Humans; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D018807:Polymorphism, Single-Stranded Conformational; 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; D004247:DNA