Autosomal dominant
hypocalcemia can be caused by activating mutations of the
calcium-sensing receptor (CaSR) gene. We experienced two patients (proband and her daughter) with
hypocalcemia caused by a missense mutation of the CaSR gene. The proband, aged 25, showed
hypocalcemia and
hypoparathyroidism from infancy. She had been diagnosed as having
idiopathic hypoparathyroidism and had been treated with
calcitriol. She gave birth to a female infant at age 24 years. Her daughter was found to have
hypocalcemia (Ca, 6.6mg/dl), without seizure or
tetany, when she was 7 months old.
DNA analysis of their CaSR genes showed a novel heterozygous mutation at
codon 129 (TGC-to-AGC) with substitution of
cysteine for
serine (C129S). Familial examination revealed that this mutation had occurred de-novo in the proband. Wild-type and niutant (C129S) CaSR
cDNA were transfected into HEK293 cells, and intracellular
calcium concentrations were measured with a fluorescent
calcium indicator. HEK cells transfected with the C129S mutant CaSR gene showed a larger increase in intracellular
calcium concentration in response to the change in the extracellular
calcium concentration than HEK cells transfected with the wild-type receptor. We conclude that the C129S mutation in the CaSR gene observed in these patients causes autosomal dominant
hypocalcemia.