AUTOSOMAL-DOMINANT HYPOCALCEMIA CAUSED BY A CA2-SENSING RECEPTOR GENEMUTATION()

Defects in the human Ca2+-sensing receptor gene have recently been sho wn to cause familial hypocalciuric hypercalcaemia and neonatal severe hyperparathyroidism. We now demonstrate that a missense mutation (Glu1 28Ala) in this gene causes familial hypocalcaemia in affected members of one family. Xenopus oocytes expressing the mutant receptor exhibit a larger increase in inositol 1,4,5-triphosphate in response to Ca2+ t han oocytes expressing the wild-type receptor. We conclude that this e xtracellular domain mutation increases the receptor's activity at low Ca2+ concentrations, causing hypocalcaemia in patients heterozygous fo r such a mutation.