Nature Genetics
14, 174 - 176 (1996)
doi:10.1038/ng1096-174
Identical mutations in three different fibroblast growth factor receptor genes in autosomal dominant craniosynostosis syndromesGary A. Bellus1, 2, Karin Gaudenz3, Elaine H. Zackai3, Lome A. Clarke4, Jinny Szabo1, Clair A. Francomano1, 2
& Maximilian Muenke3, 5
1Medical Genetics Branch, National Center for Human Genome Research, National Institutes of Health, Bethesda, Maryland 20892, USA
2Center for Medical Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA
3The Children's Hospital of Philadelphia, Division of Human Genetics and Molecular Biology, Departments of Pediatrics and Genetics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-4399, USA
4Department of Medical Genetics, British Columbia Institute for Child and Family Health, Vancouver, British Columbia V5Z-4H4, Canada
5e-mail: muenke@mail.med.upenn.edu Pfeiffer syndrome (PS; McKusick MIM 101600) is an autosomal dominant craniosynostosis syndrome with characteristic craniofacial anomalies and broad thumbs and big toes1,2. We have previously demonstrated genetic heterogeneity in PS and mapped a gene to chromosome 8 (ref. 3) and a second to chromosome 10 (ref. 4). The gene on chromosome 8 is the fibroblast growth factor receptor 1 (FGFR1) with a common mutation (C755G) predicting a Pro252Arg substitution5. The gene on chromosome 10 is FGFR2 with several different mutations causing sporadic and familial PS 4,6,7,8 (Table 1). We report a recurrent single point mutation in the FGFR3 gene, located on chromosome 4p, in ten unrelated families with craniosynostosis syndromes. This mutation (C749G) predicts a Pro250Arg amino acid substitution in the extracellular domain of the FGFR3 protein. Interestingly, this common mutation occurs precisely at the analogous position within the FGFR3 protein as the mutations in FGFR1 (Pro252Arg) and FGFR2 (Pro253Arg) previously reported in Pfeiffer5 and Apert9 syndromes, respectively.
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