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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 TW/57gene 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.

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Author notes

    • Vincent El Ghouzzi
    • , Martine Le Merrer
    • , Fabienne Perrin-Schmitt
    •  & Elisabeth Lajeunie

    V.E.G., M.L.M., F.R-S. &E.L. contributed equally to this work.

Affiliations

  1. Unité de Recherches sur les Handicaps Génétiques de I'Enfant INSERM U-393, Institut Necker, 149 rue de Sèvres, 75743 Paris Cedex 15, France.

    • Vincent El Ghouzzi
    • , Martine Le Merrer
    • , Elisabeth Lajeunie
    • , Paule Benit
    • , Dominique Renier
    • , Arnold Munnich
    •  & Jacky Bonaventure
  2. LGME-CNRS, INSERM U-184,11 rueHumann, 67085 Strasbourg, France.

    • Fabienne Perrin-Schmitt
    • , Patrice Bourgeois
    •  & Anne-Laure Bolcato-Bellemin
  3. All correspondence should be addressed to J.B. or F.P.-S.

    • Fabienne Perrin-Schmitt
    •  & Jacky Bonaventure

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DOI

https://doi.org/10.1038/ng0197-42

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