A novel mutation in Ca2+-sensing receptor gene in familial hypocalciuric hypercalcemia

Missense mutations in the calcium-sensing receptor (CaSR) gene have previou sly been identified in patients with familial hypocalciuric hypercalcemia. (FHH) and neonatal severe hyperparathyroidism. We identified a newborn with hypercalcemia in our hospital by mass screening. The family members were s tudied, and we found a novel CaSR missense mutation with polymerase chain r eaction single-strand conformational polymorphism analysis. The mother, gra ndmother, and aunt of the baby all had FHH. A heterozygous missense mutatio n in exon 6 that substitutes a glutamic acid for the glycine at codon 557 ( Gly557Glu), which corresponds to the extracellular domain of CaSR, was iden tified and shown to cosegregate with the disease. Identification of the mut ation responsible for the FHH phenotype in this family may facilitate rapid testing of individuals at risk for FHH.