Fibroblast growth factor receptor 3 and the human chondrodysplasias

Heterozygous mutations of the gene encoding the fibroblast growth factor receptor 3 (FGFR3) have been found in persons with achondroplasia, thanatophoric dysplasia, and hypochondroplasia. They exhibit considerable genetic homogeneity, and specific mutations strongly correlate with the clinical severity of disease. The mutations activate the FGFR3 by promoting dimerization, by stimulating intrinsic tyrosine kinase activity, and perhaps by altering ligand and dimerization specificity. The downstream signals regulate events in the growth plate, ultimately inhibiting linear bone growth.