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. 1995 May;56(5):1075–1079.

Mutations in the Human Ca2+-Sensing-Receptor Gene That Cause Familial Hypocalciuric Hypercalcemia

Yah-Huei Wu Chou, Martin R Pollak, Maria L Brandi, Goran Toss, H Arnqvist, A Brew Atkinson, Socrates E Papapoulos, Stephen Marx, Edward M Brown, J G Seidman, Christine E Seidman
PMCID: PMC1801464  PMID: 7726161

Abstract

We report five novel mutations in the human Ca2+-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 Ca2+-sensing receptor's large extracellular domain. In three families with FHH linked to the Ca2+-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 Ca2+-sensing-receptor gene can cause FHH.

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Selected References

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