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HelpTest ID: CASRG CASR Full Gene Sequencing with Deletion/Duplication, Varies
Ordering Guidance
Targeted testing for familial variants (also called site-specific or known mutations testing) is available for the genes on this panel. See FMTT / Familial Variant, Targeted Testing, Varies. To obtain more information about this testing option, call 800-533-1710.
Testing for the CASR gene as part of a customized panel is available. For more information, see CGPH / Custom Gene Panel, Hereditary, Next-Generation Sequencing, Varies.
Shipping Instructions
Specimen preferred to arrive within 96 hours of collection.
Specimen Required
Patient Preparation: A previous bone marrow transplant from an allogenic donor will interfere with testing. Call 800-533-1710 for instructions for testing patients who have received a bone marrow transplant.
Container/Tube:
Preferred: Lavender top (EDTA) or yellow top (ACD)
Acceptable: Any anticoagulant
Specimen Volume: 3 mL
Collection Instructions:
1. Invert several times to mix blood.
2. Send whole blood specimen in original tube. Do not aliquot.
Specimen Stability Information: Ambient (preferred)/Refrigerated
Forms
1. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file. The following documents are available:
-Informed Consent for Genetic Testing (T576)
-Informed Consent for Genetic Testing (Spanish) (T826)
2. Hereditary Renal Genetic Testing Patient Information (T918)
3. If not ordering electronically, complete, print, and send a Renal Diagnostics Test Request (T830) with the specimen.
Useful For
Providing a genetic evaluation of individuals with a personal or family history of familial hypocalciuric hypercalcemia, neonatal severe primary hyperparathyroidism, or autosomal dominant hypoparathyroidism (autosomal dominant hypocalcemia)
Establishing a diagnosis of familial hypocalciuric hypercalcemia, neonatal severe primary hyperparathyroidism, or autosomal dominant hypoparathyroidism (autosomal dominant hypocalcemia)
As a part of the workup for patients with primary hyperparathyroidism, idiopathic hypoparathyroidism, and Bartter syndrome
Genetics Test Information
This test utilizes next-generation sequencing to detect single nucleotide, deletion-insertion, and copy number variants in the CASR gene, which is associated with autosomal dominant familial hypocalciuric hypercalcemia, autosomal dominant and autosomal recessive neonatal severe primary hyperparathyroidism, autosomal dominant hypocalcemia (hypoparathyroidism), and autosomal dominant hypocalcemia with Bartter syndrome. See Method Description for additional details.
Identification of a disease-causing variant may assist with diagnosis, prognosis, clinical management, familial screening, and genetic counseling for autosomal dominant familial hypocalciuric hypercalcemia, autosomal dominant and autosomal recessive neonatal severe primary hyperparathyroidism, autosomal dominant hypoparathyroidism (also known as autosomal dominant hypocalcemia), and autosomal dominant hypoparathyroidism with features of Bartter syndrome.
Method Name
Sequence Capture and Next-Generation Sequencing (NGS)
Reporting Name
CASR Full Gene AnalysisSpecimen Type
VariesSpecimen Minimum Volume
1 mL
Specimen Stability Information
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Varies | Varies | ||
Clinical Information
The extracellular G-protein-coupled calcium-sensing receptor (CASR) is an essential component of calcium homeostasis. CASR is expressed at high levels in the parathyroid glands and kidneys. In the parathyroid glands, an increase in serum calcium results in downregulation of gene expression of the main short-term regulator of calcium homeostasis, parathyroid hormone (PTH), as well as diminished secretion of already synthesized PTH. At the same time, kidney calcium excretion is upregulated, and sodium chloride excretion is downregulated.(1) Both activating and inactivating genetic variants have been described in CASR and result in altered calcium sensing and subsequent inappropriate PTH release relative to serum calcium concentration.
Inactivating (loss-of-function) CASR variants result in undersensing of calcium concentrations and consequent PTH overproduction. This leads to either familial hypocalciuric hypercalcemia (FHH) or neonatal severe primary hyperparathyroidism (NSPHT), depending on the severity of the functional impairment. Except for a very small percentage of cases with no apparent CASR variants, FHH is due to heterozygous inactivating CASR variants. In FHH, serum calcium levels are mildly-to-moderately elevated, PTH may be normal or only modestly elevated, phosphate is normal or slightly low, and urinary calcium excretion is low for the degree of hypercalcemia.(1) Unlike patients with primary hyperparathyroidism, the majority of FHH patients do not seem to experience adverse long-term effects from hypercalcemia and elevated PTH levels. On the other hand, NSPHT is usually caused by homozygous or compound heterozygous inactivating CASR variants but can occasionally be caused by dominant-negative heterozygous variants.(1) NSPHT presents at birth, or shortly thereafter, with severe hypercalcemia requiring urgent parathyroidectomy.
Activating (gain-of-function) CASR variants lead to oversensing of calcium, resulting in suppression of PTH secretion and consequently hypoparathyroidism and hypocalcemia. This disorder is referred to as autosomal dominant hypocalcemia or autosomal dominant hypoparathyroidism. To date, all activating variants described are functionally dominant and inheritance is therefore autosomal dominant. However, sporadic (no known genetic etiology) cases also occur. Autosomal dominant hypoparathyroidism caused by CASR variants may account for many cases of idiopathic hypoparathyroidism. In addition, while the majority of patients exhibit only hypoparathyroidism, a small subgroup has extreme gain-of-function variants. These individuals may present with additional symptoms that are consistent with type V Bartter syndrome, including hypokalemic metabolic alkalosis, hyperreninemia, hyperaldosteronism, and hypomagnesemia.(1-2)
Reference Values
An interpretive report will be provided.
Interpretation
All detected variants are evaluated according to American College of Medical Genetics and Genomics recommendations.(3) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.
Clinical Reference
1. Vahe C, Benomar K, Espiard S, et al: Diseases associated with calcium-sensing receptor. Orphanet J Rare Dis. 2017 Jan 25;12(1):19. doi: 10.1186/s13023-017-0570-z
2. Roszko KL, Bi RD, Mannstadt M: Autosomal dominant hypocalcemia (hypoparathyroidism) Types 1 and 2. Front Physiol. 2016 Oct;7:458. doi: 10.3389/fphys.2016.00458
3. Richards S, Aziz N, Bale S, et al: Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015 May;17(5):405-424
Day(s) Performed
Varies
Report Available
28 to 42 daysTest Classification
This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.CPT Code Information
81405
LOINC Code Information
| Test ID | Test Order Name | Order LOINC Value |
|---|---|---|
| CASRG | CASR Full Gene Analysis | 82534-9 |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| 618059 | Test Description | 62364-5 |
| 618060 | Specimen | 31208-2 |
| 618061 | Source | 31208-2 |
| 618062 | Result Summary | 50397-9 |
| 618063 | Result | 82939-0 |
| 618064 | Interpretation | 69047-9 |
| 618065 | Additional Results | 82939-0 |
| 618066 | Resources | 99622-3 |
| 618067 | Additional Information | 48767-8 |
| 618068 | Method | 85069-3 |
| 618069 | Genes Analyzed | 48018-6 |
| 618070 | Disclaimer | 62364-5 |
| 618071 | Released By | 18771-6 |
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