Novel missense mutation in the CASR gene in a Chinese family with familial hypocalciuric hypercalcemia.

[familial hypocalciuric hypercalcemia]

Familial hypocalciuric hypercalcemia (FHH ) is an autosomal dominant disorder characterized by asymptomatic and non-progressive hypercalcemia resulting from loss -of-function mutations of the CASR (calcium-sensing receptor ) gene located on chromosome 3 , or from mutations in two mapped but unidentified genes located on chromosome 19 .W e report a middle -aged woman incidentally found to have FHH . To determine the molecular basis of FHH in this Chinese family , we performed direct DNA sequencing of the CASR gene of the proband .We found that the proband is heterozygous for a novel missense mutation P 798 T , confirming the diagnosis of FHH . Family screening showed that all of the offspring with biochemical features of FHH have the P 798 T mutation . The mutation , P 798 T , is located in the third intracellular loop of the CASR , possibly affecting the downstream calcium sensing pathway and therefore inactivating the receptor function .The molecular basis of FHH in a Chinese family was established . The developed mutation detection assay provides a reliable method for identifying FHH carriers .