Funktionelle und klinische Relevanz von Mutationen des Calcium- Sensing- Receptors

The calcium- sensing- receptor (CaSR) is a G protein-coupled receptor, identified by Hebert and Brown in 1993. The CaSR is expressed in tissue maintaining systemic calcium homeostasis, including parathyroid cells, thyroidal C-cells, several types of kidney cells surface epithelial cells of the small and large intestines. The CaSR senses extracellular levels of calcium ion and controls calcium homeostasis regulating PTH secretion and renal calcium excretion. Mutations in the CASR gene can result in gain or loss of receptor function. Activating and inactivating mutations leading to dysfunction of the CaSR are well known. Renal loss of calcium is observed in case of an activating CaSR mutation and hypercalcemia in case of inactivating mutations. Gain of function mutations are associated to Autosomal dominant hypocalcemia, while loss of function mutations are associated to Familial hypocalciuric hypercalcemia and Neonatal severe hyperparathyroidism.