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Article
Nature Genetics  9, 165 - 172 (1995)
doi:10.1038/ng0295-165

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

Andrew O.M. Wilkie1, 2, 3, *, Sarah F. Slaney1, 2, 3, *, Michael Oldridge1, Michael D. Poole3, Geraldine J. Ashworth3, Anthony D. Hockley4, Richard D. Hayward5, David J. David6, Louise J. Pulleyn7, Paul Rutland7, Susan Malcolm7, Robin M. Winter7 & William Reardon7

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

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

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

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

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

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

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

 Correspondence should be addressed to A.O.M.W.

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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