Nature Genetics
8, 269 - 274 (1994)
doi:10.1038/ng1194-269
A common mutation in the fibroblast growth factor receptor 1 gene in Pfeiffer syndromeMaximilian Muenke1, 2, 6, Ute Schell1, Andreas Hehr1, Nathaniel H. Robin1, H. Wolfgang Losken3, Albert Schinzel4, Louise J. Pulleyn5, Paul Rutland5, William Reardon5, Sue Malcolm5
& Robin M. Winter5
1The Children's Hospital of Philadelphia and Departments of Pediatrics, Division of Human Genetics and Molecular Biology, Philadelphia, Pennsylvania 19104-4399, USA
2Genetics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-4399, USA
3Department of Plastic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA
4Institut für Medizinische Genetik, Zürich, Switzerland
5Mothercare Unit of Clinical Genetics and Molecular Genetics Unit, Institute of Child Health, London WC1N 1EH, UK
6Correspondence should be addressed to M.M. Pfeiffer syndrome (PS) is one of the classic autosomal dominant craniosynostosis syndromes with craniofacial anomalies and characteristic broad thumbs and big toes. We have previously mapped one of the genes for PS to the centromeric region of chromosome 8 by linkage analysis. Here we present evidence that mutations in the fibroblast growth factor receptor-1 (FGFR1) gene, which maps to 8p, cause one form of familial Pfeiffer syndrome. A C to G transversion in exon 5, predicting a proline to arginine substitution in the putative extracellular domain, was identified in all affected members of five unrelated PS families but not in any unaffected individuals. FGFR1 therefore becomes the third fibroblast growth factor receptor to be associated with an autosomal dominant skeletal disorder.
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