A familial syndrome of hypocalcemia with hypercalciuria due to mutations in the calcium-sensing receptor.

@article{Pearce1996AFS,
  title={A familial syndrome of hypocalcemia with hypercalciuria due to mutations in the calcium-sensing receptor.},
  author={Simon H S Pearce and Catherine Williamson and Olga Kifor and Mei Bai and Malcolm G. Coulthard and M Davies and N. J. Lewis-Barned and David A. McCredie and H Powell and Pat Kendall‐Taylor and Edward Meigs Brown and R. V. Thakker},
  journal={The New England journal of medicine},
  year={1996},
  volume={335 15},
  pages={
          1115-22
        }
}
BACKGROUND The calcium-sensing receptor regulates the secretion of parathyroid hormone in response to changes in extracellular calcium concentrations, and mutations that result in a loss of function of the receptor are associated with familial hypocalciuric hypercalcemia. Mutations involving a gain of function have been associated with hypocalcemia in two kindreds. We examined the possibility that the latter type of mutation may result in a phenotype of familial hypocalcemia with hypercalciuria… Expand
A novel mutation in the calcium-sensing receptor responsible for autosomal dominant hypocalcemia in a family with two uncommon parathyroid hormone polymorphisms.
TLDR
Results suggested that the PTH gene could act as a modifier locus of ADH, affecting the penetrance of the activating CaSR mutation described, which seems to be required for the coupling of ligand binding to the activation of intracellular signaling pathways. Expand
A family of autosomal dominant hypocalcemia with an activating mutation of calcium-sensing receptor gene.
TLDR
Monitoring of urinary Ca excretion before and during treatment of PTH-deficient hypoparathyroidism is very important, and screening of CaSR mutation should be considered in patients with relative hypercalciuria or with a family history of hypocalcemia. Expand
A novel activating mutation in calcium-sensing receptor gene associated with a family of autosomal dominant hypocalcemia.
TLDR
A novel heterozygous mutation in CaSR gene that causes lysine to asparagine substitution at codon 47 (K47N), which is in the extracellular domain of CaSR, is described and results confirm that this mutation is responsible for ADH in this family. Expand
Novel calcium-sensing receptor cytoplasmic tail deletion mutation causing autosomal dominant hypocalcemia: molecular and clinical study.
TLDR
Functional analysis suggests that the cytoplasmic tail of the CASR contains determinants that regulate the attenuation of signal transduction in patients with isolated idiopathic hypoparathyroidism. Expand
A hypocalcemic child with a novel activating mutation of the calcium-sensing receptor gene: successful treatment with recombinant human parathyroid hormone.
TLDR
PTH should be evaluated further as a treatment of autosomal dominant hypocalcemia in young patients, especially those with activating mutations of the calcium-sensing receptor (CASR) gene, being treated with oral calcium and calcitriol. Expand
Familial hypercalcemia and hypercalciuria caused by a novel mutation in the cytoplasmic tail of the calcium receptor.
TLDR
The hypercalcemic disorder of the present family is caused by an inactivating point mutation in the cytoplasmic tail of the CaR and displays clinical characteristics atypical of FHH and primary HPT. Expand
A novel gain-of-function mutation (F821L) in the transmembrane domain of calcium-sensing receptor is a cause of severe sporadic hypoparathyroidism
TLDR
Analysis of in vitro functional properties of the mutant receptor revealed a leftward shift in the concentration-response curve for the mutant compared to wild-type receptor, which is therefore a novel gain-of-function mutation which can cause severe hypoparathyroidism. Expand
Hydrochlorothiazide effectively reduces urinary calcium excretion in two Japanese patients with gain-of-function mutations of the calcium-sensing receptor gene.
Gain-of-function mutations of the calcium-sensing receptor (CaR) gene cause autosomal dominant and/or sporadic hypocalcemia with hypercalciuria. Because treatment of the hypocalcemia with vitamin DExpand
Mutations affecting G-protein subunit α11 in hypercalcemia and hypocalcemia.
TLDR
GNA11 mutations predicted disrupted protein structures, and assessment on the basis of in vitro expression showed that familial hypocalciuric hypercalcemia type 2-associated mutations decreased the sensitivity of cells expressing calcium-sensing receptors to changes in extracellular calcium concentrations, whereas autosomal dominant hypocalcemia types 1 and 2- associated mutations increased cell sensitivity. Expand
A novel activating mutation (C129S) in the calcium-sensing receptor gene in a Japanese family with autosomal dominant hypocalcemia
TLDR
It is concluded that the C129S mutation in the CaSR gene observed in these patients causes autosomal dominant hypocalcemia. Expand
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References

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TLDR
Results imply that this mutation in the human Ca(2+)-sensing receptor gene causes FHH and that the dosage of the gene defect determines disease phenotype. Expand
Clustered inactivating mutations and benign polymorphisms of the calcium receptor gene in familial benign hypocalciuric hypercalcemia suggest receptor functional domains.
TLDR
It is suggested that mutations in regulatory or intronic regions of the CaR gene may also underlie many cases of FBHH, and that these are important functional domains, probably for calcium binding and signal transduction, respectively. Expand
Mutations in the human Ca2+-sensing receptor gene cause familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
We demonstrate that mutations in the human Ca(2+)-sensing receptor gene cause familial hypocalciuric hypercalcemia (FHH) and neonatal severe hyperparathyroidism (NSHPT), two inherited conditionsExpand
Mutations in the human Ca(2+)-sensing-receptor gene that cause familial hypocalciuric hypercalcemia.
TLDR
Five novel mutations in the human Ca(2+)-sensing-receptor gene that cause familial hypocalciuric hypercalcemia (FHH) or neonatal severe hyperparathyroidism are reported and it is suggested that there are a wide range of mutations that cause FHH. Expand
Calcium-sensing receptor mutations in familial benign hypercalcemia and neonatal hyperparathyroidism.
TLDR
The single-stranded conformational polymorphism identification of CaR mutations may help in the distinction of FBH from mild primary hyperparathyroidism which can be clinically difficult. Expand
Familial Isolated Hypoparathyroidism: A Molecular Genetic Analysis of 8 Families with 23 Affected Persons
TLDR
It is concluded that FIH is a diverse group of disorders and is characterized by genetic and molecular heterogeneity, and linkage analysis using DNA polymorphisms within the PTH gene is of benefit in identifying individuals with disorders of PTH secretion or synthesis in whom DNA sequencing and expression studies of the P TH gene might succeed in establishing the molecular basis of the disease. Expand
A missense mutation in the Ca-sensing receptor gene causes familial autosomal dominant hypoparathyroidism
A large family was identified in which hypoparathyroidism was observed to segregate as an autosomal dominant trait in 3 generations. Linkage analysis using short tandem repeat polymorphisms linkedExpand
Urinary calcium excretion in familial hypocalciuric hypercalcemia. Persistence of relative hypocalciuria after induction of hypoparathyroidism.
TLDR
The greater calciuric response to ethacrynic acid than to acetazolamide or calcium infusion alone in FHH indicates that a major renal locus of abnormal calcium transport in this disorder may be the ascending limb of the loop of Henle. Expand
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TLDR
The FBH phenotype results from mutations at two separate loci on chromosomes 3q and 19p, tightly linked to the marker loci D 19S20 and D19S266. Expand
Insertion of an Alu sequence in the Ca(2+)-sensing receptor gene in familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism.
TLDR
Family members of a Nova Scotian deme expressing both FHH and NSHPT were found to be heterozygous for an abnormally large exon 7 of the CaR gene, and identification of the specific mutation responsible for the FHH/NSHPT phenotype will allow rapid testing of at-risk individuals. Expand
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