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Bent bone dysplasia-FGFR2 type, a distinct skeletal disorder, has deficient canonical FGF signaling.

Authors: Merrill, Amy E  Sarukhanov, Anna  Krejci, Pavel  Idoni, Brian  Camacho, Natalia  Estrada, Kristine D  Lyons, Karen M  Deixler, Hannah  Robinson, Haynes  Chitayat, David  Curry, Cynthia J  Lachman, Ralph S  Wilcox, William R  Krakow, Deborah 
Citation: Merrill AE, etal., Am J Hum Genet. 2012 Mar 9;90(3):550-7. doi: 10.1016/j.ajhg.2012.02.005. Epub 2012 Mar 1.
Pubmed: (View Article at PubMed) PMID:22387015
DOI: Full-text: DOI:10.1016/j.ajhg.2012.02.005

Fibroblast growth factor receptor 2 (FGFR2) is a crucial regulator of bone formation during embryonic development. Both gain and loss-of-function studies in mice have shown that FGFR2 maintains a critical balance between the proliferation and differentiation of osteoprogenitor cells. We have identified de novo FGFR2 mutations in a sporadically occurring perinatal lethal skeletal dysplasia characterized by poor mineralization of the calvarium, craniosynostosis, dysmorphic facial features, prenatal teeth, hypoplastic pubis and clavicles, osteopenia, and bent long bones. Histological analysis of the long bones revealed that the growth plate contained smaller hypertrophic chondrocytes and a thickened hypercellular periosteum. Four unrelated affected individuals were found to be heterozygous for missense mutations that introduce a polar amino acid into the hydrophobic transmembrane domain of FGFR2. Using diseased chondrocytes and a cell-based assay, we determined that these mutations selectively reduced plasma-membrane levels of FGFR2 and markedly diminished the receptor's responsiveness to extracellular FGF. All together, these clinical and molecular findings are separate from previously characterized FGFR2 disorders and represent a distinct skeletal dysplasia.

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RGD Object Information
RGD ID: 12801468
Created: 2017-04-03
Species: All species
Last Modified: 2017-04-03
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.