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Autosomal dominant hypocalcaemia caused by a Ca2+-sensing receptor gene mutation

Nature Genetics volume 8, pages 303–307 (1994)Cite this article

Abstract

Defects in the human Ca2+-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.

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Author information

Affiliations

  1. Renal, Brigham and Women's Hospital, 75 Francis Street, Boston, Massachusetts, 02115, USA

    Martin R. Pollak & Steven C. Hebert

  2. Endocrine-Hypertension, Brigham and Women's Hospital, 75 Francis Street, Boston, Massachusetts, 02115, USA

    Edward M. Brown, Olga Kifor & Ji Park

  3. Department of Internal Medicine, Eastern Virginia Medical School, Norfolk, Virginia, 23505, USA

    Herschel L. Estep

  4. Department of Pediatrics, Children's Hospital of Eastern Ontario, Ontario, Canada

    Peter N. McLaine

  5. Howard Hughes Medical Institute, Department of Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston, Massachusetts, 02115, USA

    Christine E. Seidman

  6. Department of Genetics, Harvard Medical School and the Howard Hughes Medical Institute, 200 Longwood Avenue, Boston, Massachusetts, 02115, USA

    J. G. Seidman

Authors
  1. Martin R. Pollak
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  2. Edward M. Brown
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  3. Herschel L. Estep
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  4. Peter N. McLaine
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  5. Olga Kifor
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  6. Ji Park
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  7. Steven C. Hebert
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  8. Christine E. Seidman
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  9. J. G. Seidman
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Pollak, M., Brown, E., Estep, H. et al. Autosomal dominant hypocalcaemia caused by a Ca2+-sensing receptor gene mutation. Nat Genet 8, 303–307 (1994). https://doi.org/10.1038/ng1194-303

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  • DOI: https://doi.org/10.1038/ng1194-303

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