title: Familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism associated with mutations in the human Ca2+-sensing receptor gene in three Danish families.
abstract: We screened three unrelated Danish families with familial hypocalciuric hypercalcemia (FHH) for mutations in the Ca2+-sensing receptor (CASR) gene by polymerase chain reaction amplification and DNA sequencing of exons 2-7, which include the entire coding region of the gene. In one family the affected individuals have a T-->C mutation that changes the normal arginine at codon 220 to a tryptophan. In the other two FHH families, affected individuals have the same A-->G mutation, leading to conversion of the normal glycine at codon 552 to an arginine. These results confirm that FHH can be caused by non-conservative missense mutations in the CASR gene leading to abnormal calcium homeostasis. Both mutations are located in the amino-terminal extracellular domain of the receptor, which contains the binding site for extracellular Ca2+, the CASR's principal physiological agonist.
authors.affiliation: Department of Clinical Biochemistry, Glostrup Hospital, University of Copenhagen, Denmark.
authors.forename: P
authors.initials: P
authors.lastname: Schwarz
authors.forename: N E
authors.initials: NE
authors.lastname: Larsen
authors.forename: I M
authors.initials: IM
authors.lastname: Lønborg Friis
authors.forename: K
authors.initials: K
authors.lastname: Lillquist
authors.forename: E M
authors.initials: EM
authors.lastname: Brown
authors.forename: S
authors.initials: S
authors.lastname: Gammeltoft
mesh_terms: D002118:Calcium / Q000652:urine*; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D006934:Hypercalcemia / Q000235:genetics* / Q000652:urine*; D006961:Hyperparathyroidism / Q000235:genetics*; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface; D002118:Calcium