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Article
Nature Genetics  8, 98 - 103 (1994)
doi:10.1038/ng0994-98

Mutations in the fibroblast growth factor receptor 2 gene cause Crouzon syndrome

William Reardon3, Robin M. Winter1, Paul Rutland1, Louise J. Pulleyn1, Barry M. Jones2 & Sue Malcolm1

  1Mothercare Unit of Clinical Genetics and Fetal Medicine and Molecular Genetics Unit, Institute of Child Health, 30 Guilford St., London WC1N 1EH, UK

  2Dept of Plastic and Reconstructive Surgery, Great Ormond St. Hospital For Children, London WC1N 3JN, UK

  3Correspondence should be addressed to W.R.

Crouzon syndrome is an autosomal dominant condition causing premature fusion of the cranial sutures (craniosynostosis) and maps to chromosome 10q25−q26. We now present evidence that mutations in the fibroblast growth factor receptor 2 gene (FGFR2) cause Crouzon syndrome. We found SSCP variations in the B exon of FGFR2 in nine unrelated affected individuals as well as complete cosegregation between SSCP variation and disease in three unrelated multigenerational families. In four sporadic cases, the normal parents did not have SSCP variation. Finally, direct sequencing has revealed specific mutations in the B exon in all nine sporadic and familial cases, including replacement of a cysteine in an immunoglobulin-like domain in five patients.

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Nature Genetics
ISSN: 1061-4036
EISSN: 1546-1718
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