Autosomal dominant hypocalcaemia caused by a Ca(2+)-sensing receptor gene mutation

Nat Genet. 1994 Nov;8(3):303-7. doi: 10.1038/ng1194-303.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Calcium / blood*
  • DNA Mutational Analysis
  • DNA, Complementary / genetics
  • Female
  • Genes, Dominant*
  • Heterozygote
  • Homeostasis
  • Humans
  • Hypocalcemia / genetics*
  • Inositol 1,4,5-Trisphosphate / metabolism
  • Lod Score
  • Male
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Oocytes
  • Pedigree
  • Point Mutation*
  • Receptors, Calcium-Sensing
  • Receptors, Cell Surface / genetics*
  • Recombinant Fusion Proteins / metabolism
  • Tetany / genetics
  • Xenopus laevis


  • DNA, Complementary
  • Receptors, Calcium-Sensing
  • Receptors, Cell Surface
  • Recombinant Fusion Proteins
  • Inositol 1,4,5-Trisphosphate
  • Calcium