title: Autosomal dominant hypocalcaemia caused by a Ca(2+)-sensing receptor gene mutation.
abstract: Defects in the human Ca(2+)-sensing receptor gene have recently been shown to cause familial hypocalciuric hypercalcaemia and neonatal severe hyperparathyroidism. We now demonstrate that a missense mutation (Glu128Ala) in this gene causes familial hypocalcaemia in affected members of one family. Xenopus oocytes expressing the mutant receptor exhibit a larger increase in inositol 1,4,5-triphosphate in response to Ca2+ than oocytes expressing the wild-type receptor. We conclude that this extracellular domain mutation increases the receptor's activity at low Ca2+ concentrations, causing hypocalcaemia in patients heterozygous for such a mutation.
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115.
authors.forename: M R
authors.initials: MR
authors.lastname: Pollak
authors.forename: E M
authors.initials: EM
authors.lastname: Brown
authors.forename: H L
authors.initials: HL
authors.lastname: Estep
authors.forename: P N
authors.initials: PN
authors.lastname: McLaine
authors.forename: O
authors.initials: O
authors.lastname: Kifor
authors.forename: J
authors.initials: J
authors.lastname: Park
authors.forename: S C
authors.initials: SC
authors.lastname: Hebert
authors.forename: C E
authors.initials: CE
authors.lastname: Seidman
authors.forename: J G
authors.initials: JG
authors.lastname: Seidman
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002118:Calcium / Q000097:blood*; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D005799:Genes, Dominant; D006579:Heterozygote; D006706:Homeostasis; D006801:Humans; D006996:Hypocalcemia / Q000235:genetics*; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D008126:Lod Score; D008297:Male; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009865:Oocytes; D010375:Pedigree; D017354:Point Mutation; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013746:Tetany / Q000235:genetics; D014982:Xenopus laevis
chemical_list: D018076:DNA, Complementary; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium