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Mutations in TWIST, a basic helix–loop–helix transcription factor, in Saethre-Chotzen syndrome

Nature Genetics volume 15, pages 36–41 (1997)Cite this article

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.

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Authors and Affiliations

  1. Departments of Pediatrics, Medicine, and Surgery, Center for Medical Genetics, The Johns Hopkins School of Medicine, CMSC 10-04, 600 North Wolfe Street, Baltimore, Maryland, 21287-3914, USA

    Timothy D. Howard, William A. Paznekas, Lydia C. Chiang & Ethylin Wang Jabs

  2. Genome Technology Branch, National Center for Human Genome Research, National Institutes of Health, Bethesda, Maryland, 20892, USA

    Eric D. Green

  3. Genome Therapeutics Corporation, Collaborative Research Division, 1365 Main Street, Waltham, Massachusetts, 02154, USA

    Nancy Ma

  4. Departamento de Genética, Hospital Infantilde Mexico, “Federico Gómez,”, Dr. MárquezNum 162, Col. Doctores C.R, México City, 06720, México

    Rosa Isela Ortiz De Luna, Costanza Garcia Delgado & Mario Gonzalez-Ramos

  5. Department of Pediatrics, Division of Clinical Genetics, Sinai Hospital, 5101 LanierAve., Baltimore, Maryland, 21215, USA

    Antoine D. Kline

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  1. Timothy D. Howard
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Howard, T., Paznekas, W., Green, E. et al. Mutations in TWIST, a basic helix–loop–helix transcription factor, in Saethre-Chotzen syndrome. Nat Genet 15, 36–41 (1997). https://doi.org/10.1038/ng0197-36

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