Summary
Jansen's metaphyseal chondrodysplasia (JMC) is a rare autosomal dominant disorder characterized by short-limbed dwarfism and severe, agonist-independent hypercalcemia. Four different mutations in the gene encoding the PTH/PTHrP receptor (PTHR1) have been identified in several unrelated JMC patients. When expressed in vitro, these mutant PTHR1s cause agonist-independent cAMP accumulation. The PTHR1, a member of a distinct family of G protein-coupled receptors, is abundantly expressed in kidney and bone, where it mediates the PTH-dependent regulation of calcium and phosphorus, and in the growth plate, where it mediates the PTHrP-dependent regulation chondrocyte growth and differentiation. The presence of PTHR1 mutations that induce constitutive activity thus provides a plausible explanation for the abnormal regulation of mineral ion homeostasis and growth plate development in JMC. *Authors: Dr. C. Silve and Dr. H. Jüppner (January 2005)*.
