title: A novel activating mutation (C129S) in the calcium-sensing receptor gene in a Japanese family with autosomal dominant hypocalcemia.
abstract: 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.
authors: Department of Pediatrics, Developmental Medicine, Osaka University Graduate School of Medicine, Suita, Japan.
authors: H
authors: H
authors: Hirai
authors: S
authors: S
authors: Nakajima
authors: A
authors: A
authors: Miyauchi
authors: K
authors: K
authors: Nishimura
authors: N
authors: N
authors: Shimizu
authors: M
authors: M
authors: Shima
authors: T
authors: T
authors: Michigami
authors: K
authors: K
authors: Ozono
authors: S
authors: S
authors: Okada
mesh_terms: D000328:Adult; D001483:Base Sequence; D005260:Female; D005799:Genes, Dominant; D006801:Humans; D006996:Hypocalcemia / Q000208:ethnology / Q000235:genetics*; D007564:Japan; D008297:Male; D009154:Mutation; D010375:Pedigree; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface