title: Mutations that cause osteoglophonic dysplasia define novel roles for FGFR1 in bone elongation.
abstract: Activating mutations in the genes for fibroblast growth factor receptors 1-3 (FGFR1-3) are responsible for a diverse group of skeletal disorders. In general, mutations in FGFR1 and FGFR2 cause the majority of syndromes involving craniosynostosis, whereas the dwarfing syndromes are largely associated with FGFR3 mutations. Osteoglophonic dysplasia (OD) is a "crossover" disorder that has skeletal phenotypes associated with FGFR1, FGFR2, and FGFR3 mutations. Indeed, patients with OD present with craniosynostosis, prominent supraorbital ridge, and depressed nasal bridge, as well as the rhizomelic dwarfism and nonossifying bone lesions that are characteristic of the disorder. We demonstrate here that OD is caused by missense mutations in highly conserved residues comprising the ligand-binding and transmembrane domains of FGFR1, thus defining novel roles for this receptor as a negative regulator of long-bone growth.
authors.affiliation: Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: White
authors.forename: Jose M
authors.initials: JM
authors.lastname: Cabral
authors.forename: Siobhan I
authors.initials: SI
authors.lastname: Davis
authors.forename: Tonya
authors.initials: T
authors.lastname: Fishburn
authors.forename: Wayne E
authors.initials: WE
authors.lastname: Evans
authors.forename: Shoji
authors.initials: S
authors.lastname: Ichikawa
authors.forename: Joanna
authors.initials: J
authors.lastname: Fields
authors.forename: Xijie
authors.initials: X
authors.lastname: Yu
authors.forename: Nick J
authors.initials: NJ
authors.lastname: Shaw
authors.forename: Neil J
authors.initials: NJ
authors.lastname: McLellan
authors.forename: Carole
authors.initials: C
authors.lastname: McKeown
authors.forename: David
authors.initials: D
authors.lastname: Fitzpatrick
authors.forename: Kai
authors.initials: K
authors.lastname: Yu
authors.forename: David M
authors.initials: DM
authors.lastname: Ornitz
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Econs
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D001848:Bone Diseases, Developmental / Q000235:genetics*; D004252:DNA Mutational Analysis; D005145:Face / Q000002:abnormalities*; D006801:Humans; D007621:Karyotyping; D008297:Male; D008445:Maxillofacial Development / Q000235:genetics; D008875:Middle Aged; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010375:Pedigree; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D051496:Receptor, Fibroblast Growth Factor, Type 1; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics*; D012886:Skull / Q000002:abnormalities*
chemical_list: D017468:Receptors, Fibroblast Growth Factor; C496348:FGFR1 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1