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

Abstract Background 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. Methods We 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. Results We found that the proband is heterozygous for a novel missense mutation P798T, confirming the diagnosis of FHH. Family screening showed that all of the offspring with biochemical features of FHH have the P798T mutation. The mutation, P798T, is located in the third intracellular loop of the CASR , possibly affecting the downstream calcium sensing pathway and therefore inactivating the receptor function. Conclusions The molecular basis of FHH in a Chinese family was established. The developed mutation detection assay provides a reliable method for identifying FHH carriers.