title: Identical mutations in three different fibroblast growth factor receptor genes in autosomal dominant craniosynostosis syndromes.
abstract: Pfeiffer syndrome (PS; McKusick MIM 101,600) is an autosomal dominant craniosynostosis syndrome with characteristic craniofacial anomalies and broad thumbs and big toes. 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 substitution. The gene on chromosome 10 is FGFR2 with several different mutations causing sporadic and familial PS (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 Pfeiffer and Apert syndromes, respectively.
authors.affiliation: Medical Genetics Branch, National Center for Human Genome Research, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: G A
authors.initials: GA
authors.lastname: Bellus
authors.forename: K
authors.initials: K
authors.lastname: Gaudenz
authors.forename: E H
authors.initials: EH
authors.lastname: Zackai
authors.forename: L A
authors.initials: LA
authors.lastname: Clarke
authors.forename: J
authors.initials: J
authors.lastname: Szabo
authors.forename: C A
authors.initials: CA
authors.lastname: Francomano
authors.forename: M
authors.initials: M
authors.lastname: Muenke
mesh_terms: D000168:Acrocephalosyndactylia / Q000235:genetics*; D000595:Amino Acid Sequence; D003394:Craniofacial Dysostosis / Q000235:genetics; D003398:Craniosynostoses / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005799:Genes, Dominant / Q000235:genetics; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D017354:Point Mutation / Q000235:genetics*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D051497:Receptor, Fibroblast Growth Factor, Type 2; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics*; D013577:Syndrome
chemical_list: D017468:Receptors, Fibroblast Growth Factor; C496353:FGFR2 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051497:Receptor, Fibroblast Growth Factor, Type 2