The calcium-sensing receptor (CaSR) is a G-protein-coupled receptor that plays 
an essential role in maintaining calcium homeostasis. In the present study, we 
analyzed the CaSR gene in a Korean family with familial hypocalciuric 
hypercalcemia (FHH). Genetic studies were performed by direct sequence analysis 
of the CaSR gene in genomic DNA obtained from peripheral leukocytes. A novel 
heterozygous G to T substitution at nucleotide position 1711 in exon 6, 
resulting in the G571W mutation, was identified in the CaSR gene in a 
26-year-old female with asymptomatic hypercalcemia, a low calcium/creatinine 
clearance ratio, and normal intact parathyroid hormone. To study CaSR 
expression, the mutation was introduced by site-directed mutagenesis into a 
wild-type (WT) CaSR-expressing pCR3.1 vector, and COS-7 cells were transfected 
with either the WT or mutant CaSR-containing vector. Transfected cells loaded 
with Fura-2/AM, a fluorescent indicator of Ca2+, were assessed for CaSR function 
by the change in intracellular calcium [as measured by the 340 nm/380 nm 
fluorescence intensity ratio (F340/F380)] made in response to challenge with 
extracellular Ca2+. Both WT and G571W cells had equivalent amounts of CaSR 
protein in the cell membrane. However, after challenge with extracellular Ca2+, 
cells transfected with G571W CaSR responded with a lower F340/F380 ratio than 
those transfected with WT CaSR and showed decreased sensitivity to extracellular 
Ca2+ concentrations. The G571W mutation had therefore impaired the CaSR 
function. In conclusion, we identified a novel loss-of-function mutation, G571W, 
in the CaSR gene in a Korean family with FHH.