title: Mutations in the human Ca(2+)-sensing-receptor gene that cause familial hypocalciuric hypercalcemia.
abstract: We report five novel mutations in the human Ca(2+)-sensing-receptor gene that cause familial hypocalciuric hypercalcemia (FHH) or neonatal severe hyperparathyroidism. Each gene defect is a missense mutation (228Arg-->Gln, 139Thr-->Met, 144Gly-->Glu, 63Arg-->Met, and 67Arg-->Cys) that encodes a nonconservative amino acid alteration. These mutations are each predicted to be in the Ca(2+)-sensing receptor's large extracellular domain. In three families with FHH linked to the Ca(2+)-sensing-receptor gene on chromosome 3 and in unrelated individuals probands with FHH, mutations were not detected in protein-coding sequences. On the basis of these data and previous analyses, we suggest that there are a wide range of mutations that cause FHH. Mutations that perturb the structure and function of the extracellular or transmembrane domains of the receptor and those that affect noncoding sequences of the Ca(2+)-sensing-receptor gene can cause FHH.
authors.affiliation: Liver Research Unit, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
authors.forename: Y H
authors.initials: YH
authors.lastname: Chou
authors.forename: M R
authors.initials: MR
authors.lastname: Pollak
authors.forename: M L
authors.initials: ML
authors.lastname: Brandi
authors.forename: G
authors.initials: G
authors.lastname: Toss
authors.forename: H
authors.initials: H
authors.lastname: Arnqvist
authors.forename: A B
authors.initials: AB
authors.lastname: Atkinson
authors.forename: S E
authors.initials: SE
authors.lastname: Papapoulos
authors.forename: S
authors.initials: S
authors.lastname: Marx
authors.forename: E M
authors.initials: EM
authors.lastname: Brown
authors.forename: J G
authors.initials: JG
authors.lastname: Seidman
mesh_terms: D002118:Calcium / Q000378:metabolism / Q000652:urine; D006801:Humans; D006934:Hypercalcemia / Q000235:genetics*; D017354:Point Mutation; D011487:Protein Conformation; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface / Q000235:genetics*
chemical_list: D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface; D002118:Calcium