Calcium-Sensing Receptor (CASR) Gene Sequencing Analysis

CPT: 81405
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Test Details

Synonyms

  • CASR gene

Use

CASR encodes the calcium sensing receptor (CaSR) which, when activated (1) inhibits secretion of parathyroid hormone (PTH), (2) stimulates calcitonin release from the thyroid, and (3) stimulates urinary calcium excretion. CASR mutations can result in calcium dysregulation:

• Heterozygous inactivating mutations cause familial hypocalciuric hypercalcemia (FHH)

• Homozygous inactivating mutations cause neonatal severe hyperparathyroidism (NSHPT)

• Heterozygous activating mutations cause autosomal dominant hypocalcemia (ADH) or Bartter syndrome type V

Detection rates range from 18-70% for hypercalcemia and approximately 40% for hypocalcemia, as there are additional genes that affect calcium regulation.

Identification of CASR mutations can be used to:

• Determine the cause of hypercalcemia in patients considering parathyroid surgery (CASR mutations are not usually associated with PTH-producing tumors)

• Confirm the diagnosis of NSHPT, leading to urgent parathyroidectomy

• Identify individuals with ADH who are at risk for developing kidney stones with vitamin D supplements

• Influence treatment options with calcimimetic or calcilytic therapies

Limitations

Mutations that are not in exons 2 through 7 are not analyzed and will not be detected. Polymorphisms at PCR primer target sites may lead to false-negative results. This method will not detect changes in CASR gene copy number or in other genes that affect calcium homeostasis.

This test was developed and its performance characteristics determined by LabCorp. It has not been cleared or approved by the US Food and Drug Administration (FDA).

Methodology

Polymerase chain reaction (PCR) and Sanger sequencing of targeted CASR exons, gel electrophoresis

Specimen Requirements

Specimen

Whole blood

Volume

3.0 mL

Minimum Volume

1.0 mL

Container

Lavender-top (EDTA) tube or yellow-top (ACD) tube

Storage Instructions

Room temperature

Causes for Rejection

Serum or plasma specimens; frozen samples; hemolyzed samples

Clinical Information

Special Instructions

This assay is currently not available in New York.

Testing is performed at Esoterix Endocrinology Laboratory.

References

Cole DE, Yun FH, Wong BY, et al. Calcium-sensing receptor mutations and denaturing high performance liquid chromatography. J Mol Endocrinol. 2009 Apr;42(4):331-339.19179454
Hannan FM, Nesbit MA, Zhang C, et al. Identification of 70 calcium-sensing receptor mutations in hyper- and hypo-calcaemic patients: evidence for clustering of extracellular domain mutations at calcium-binding sites. Hum Mol Genet. 2012 Jun 15;21(12):2768-2778.22422767
Lienhardt A, Bai M, Lagarde JP, et al. Activating mutations of the calcium-sensing receptor: management of hypocalcemia. J Clin Endocrinol Metab. 2001 Nov;86(11):5313-5323.11701698
Nissen PH, Christensen SE, Heickendorff L, Brixen K, Mosekilde L. Molecular genetic analysis of the calcium sensing receptor gene in patients clinically suspected to have familial hypocalciuric hypercalcemia: phenotypic variation and mutation spectrum in a Danish population. J Clin Endocrinol Metab. 2007 Nov;92(11):4373-4379.17698911
Pidasheva S, D'Souza-Li L, Canaff L, Cole DE, Hendy GN. CASRdb: calcium-sensing receptor locus-specific database for mutations causing familial (benign) hypocalciuric hypercalcemia, neonatal severe hyperparathyroidism, and autosomal dominant hypocalcemia. Hum Mutat. 2004 Aug;24(2):107-111.15241791
Pollak MR, Chou YH, Marx SJ, et al. Familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism: effects of mutant gene dosage on phenotype. J Clin Invest. 1994 Mar;93(3):1108-1112.8132750
Vahe C, Benomar K, Espiard S, et al. Diseases associated with calcium-sensing receptor. Orphanet J Rare Dis. 2017 Jan 25;12(1):19.28122587

LOINC® Map

Order Code Order Code Name Order Loinc Result Code Result Code Name UofM Result LOINC
504513 CASR Gene Sequencing 504514 CASR Gene Sequencing 82534-9
504513 CASR Gene Sequencing 504516 Result 19146-0
504513 CASR Gene Sequencing 504517 Interpretation 50397-9
504513 CASR Gene Sequencing 504518 Comments 8251-1
504513 CASR Gene Sequencing 504520 References 75608-0
504513 CASR Gene Sequencing 000000 Esoterix Informed Consent Req N/A
504513 CASR Gene Sequencing 504521 CASR Gene Sequencing N/A

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