POINT MUTATIONS OF THE HUMAN PARATHYROID CALCIUM RECEPTOR GENE ARE NOT RESPONSIBLE FOR NON-SUPPRESSIBLE RENAL HYPERPARATHYROIDISM

The calcium-dependent secretion of parathyroid hormone (PTH) is mediat ed through an extracellular G protein-coupled calcium receptor (CaR). Inactivating point mutations of this receptor have been found in famil ial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidis m. These diseases feature a decreased calcium sensitivity of the parat hyroid glands, resulting in a rightward shift of the Ca2+-PTH relation ship. Severe, non-suppressible renal hyperparathyroidism (rHPT) is oft en characterized by similar setpoint shifts to the right. Thus, point mutations of the CaR gene could contribute to non-suppressible rHPT. W e examined genomic DNA of hyperplastic or mainly nodular tissues of 39 parathyroids from 25 rHPT-patients with resistance to calcitriol ther apy. Amplification of the six exons of the CaR gene was followed by si ngle-strand conformation polymorphism (SSCP) analysis. DNA sequencing was performed where band shifts were observed. No point mutations in t he coding sequence of the CaR gene were detected using the PCR-SSCP st rategy. Point mutations in the coding regions of the CaR gene probably play no role in the evolution of renal HPT and are not responsible fo r the calcitriol resistance of PTH secretion.