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Calcium Sensing Receptor Gene Mutation

The calcium sensing receptor (CASR) plays an important role in calcium homeostasis. CASR is present at particularly high levels in the parathyroid glands and kidneys.

Binding of calcium by CASR in the parathyroid glands results in down regulation of  parathyroid hormone (PTH) synthesis, while binding of calcium to the CASR in the kidneys results in upregulation of  renal calcium excretion. These simultaneous opposite reactions lead to tight control of plasma calcium levels.

Familial hypocalciuric hypercalcemia is caused by various autosomal-dominant loss-of-function mutations in the gene coding for the CASR. This disease is often initially misdiagnosed as hyperparathyroidism, but unlike hyperparathyroidism, does not require parathyroidectomy. To date over 100 different alterations in the CASR gene have been identified. Loss of function mutations in the CASR gene result in under-sensing of calcium concentrations and overproduction and secretion of PTH. Familial hypocalciuric hypercalcemia is characterized by mildly-to-moderately elevated plasma calcium levels, normal or slightly low phosphate levels, and urinary calcium excretion that is low for the degree of hypercalcemia. PTH remains within the reference range or is modestly elevated.

Activating mutations lead to oversensing of calcium, resulting in suppression of PTH secretion and consequently hypoparathyroidism. All of the activating mutations described so far have been inherited in an autosomal dominant manner.

A CASR mutation should be identified in an affected family member before predictive testing of family members is ordered. CASR mutations are detected by DNA sequencing .

Specimen requirement is a lavender top(EDTA) tube of whole blood.


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