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Apert syndrome results from localized mutations of FGFR2 and is allelic with Crouzon syndrome

Nature Genetics volume 9, pages 165–172 (1995)Cite this article

Abstract

Apert syndrome is a distinctive human malformation comprising craniosynostosis and severe syndactyly of the hands and feet. We have identified specific missense substitutions involving adjacent amino acids (Ser252Trp and Pro253Arg) in the linker between the second and third extracellular immunoglobulin (Ig) domains of fibroblast growth factor receptor 2 (FGFR2) in all 40 unrelated cases of Apert syndrome studied. Crouzon syndrome, characterized by craniosynostosis but normal limbs, was previously shown to result from allelic mutations of the third Ig domain of FGFR2. The contrasting effects of these mutations provide a genetic resource for dissecting the complex effects of signal transduction through FGFRs in cranial and limb morphogenesis.

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Authors and Affiliations

  1. Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK

    Andrew O.M. Wilkie, Sarah F. Slaney & Michael Oldridge

  2. Department of Clinical Genetics, Churchill Hospital, Oxford, OX37LJ, UK

    Andrew O.M. Wilkie & Sarah F. Slaney

  3. Oxford Craniofacial Unit, The Radcliffe Infirmary NHS Trust, Oxford, OX2 6HE, UK

    Andrew O.M. Wilkie, Sarah F. Slaney, Michael D. Poole & Geraldine J. Ashworth

  4. West Midlands Craniofacial Unit, Queen Elizabeth and Children's Hospitals, Birmingham, B16 8ET, UK

    Anthony D. Hockley

  5. Craniofacial Unit, Great Ormond Street Hospital for Children NHS Trust, London, WC1N3JH, UK

    Richard D. Hayward

  6. Australian Craniofacial Unit, Women's and Children's Hospital, North Adelaide, South Australia, 5006

    David J. David

  7. Mothercare Unit of Clinical Genetics and Fetal Medicine and Molecular Genetics Unit, Institute of Child Health, London, WC1N 1EH, UK

    Louise J. Pulleyn, Paul Rutland, Susan Malcolm, Robin M. Winter & William Reardon

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Wilkie, A., Slaney, S., Oldridge, M. et al. Apert syndrome results from localized mutations of FGFR2 and is allelic with Crouzon syndrome. Nat Genet 9, 165–172 (1995). https://doi.org/10.1038/ng0295-165

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