Bent Bone Dysplasia-FGFR2 type, a Distinct Skeletal Disorder, Has Deficient Canonical FGF Signaling

Warning

This publication doesn't include Faculty of Medicine. It includes Faculty of Science. Official publication website can be found on muni.cz.

Authors

MERRILL A.E. SARUKHANOV A. KREJČÍ Pavel IDONI B. CAMACHO N. ESTRADA K.D. LYONS K.M. DEIXLER H. ROBINSON H. CHITAYAT D. CURRY C.J. LACHMAN R.S. WILCOX W.R. KRAKOW D.

Year of publication 2012
Type Article in Periodical
Magazine / Source The American Journal of Human Genetics
MU Faculty or unit

Faculty of Science

Citation
Doi http://dx.doi.org/10.1016/j.ajhg.2012.02.005
Field Physiology
Keywords APERT-SYNDROME; LADD SYNDROME; GROWTH; MUTATIONS; RECEPTOR-2; ACTIVATION; INDUCTION; CROUZON; MOUSE; DISRUPTION
Description 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.
Related projects:

You are running an old browser version. We recommend updating your browser to its latest version.

More info