Mutations that cause osteoglophonic dysplasia define novel roles for FGFR1 in bone elongation

Kenneth E White, Jose M Cabral, Siobhan I Davis, Tonya Fishburn, Wayne E Evans, Shoji Ichikawa, Joanna Fields, Xijie Yu, Nick J Shaw, Neil J McLellan, Carole McKeown, David Fitzpatrick, Kai Yu, David M Ornitz, Michael J Econs

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Pages (from-to)361-7
Number of pages7
JournalAmerican Journal of Human Genetics
Volume76
Issue number2
DOIs
Publication statusPublished - Feb 2005

Keywords

  • Adult
  • Amino Acid Sequence
  • Bone Diseases, Developmental
  • DNA Mutational Analysis
  • Face
  • Humans
  • Karyotyping
  • Male
  • Maxillofacial Development
  • Middle Aged
  • Molecular Sequence Data
  • Mutation, Missense
  • Pedigree
  • Receptor Protein-Tyrosine Kinases
  • Receptor, Fibroblast Growth Factor, Type 1
  • Receptors, Fibroblast Growth Factor
  • Skull

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