Calcium Sensing Receptor (CASR) Gene, Known Mutation
NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
Confirming or ruling out a suspected diagnosis of familial hypocalciuric hypercalcemia in family members of affected individuals with known mutations
Confirming or ruling out a suspected diagnosis of neonatal severe primary hyperparathyroidism in family members of affected individuals with known mutations
Confirming or ruling out a suspected diagnosis of autosomal dominant hypoparathyroidism in family members of affected individuals with known mutations
Profile Information A profile is a group of laboratory tests that are ordered and performed together under a single Mayo Test ID. Profile information lists the test performed, inclusive of the test fee, when a profile is ordered and includes reporting names and individual availability.
|Test ID||Reporting Name||Available Separately||Always Performed|
|CSRMK||CASR Known Mutation||No||Yes|
Special Instructions and Forms Describes specimen collection and preparation information, test algorithms, and other information pertinent to test. Also includes pertinent information and consent forms to be used when requesting a particular test
Polymerase Chain Reaction (PCR) Amplification/DNA Sequencing
(PCR is utilized pursuant to a license agreement with Roche Molecular Systems, Inc.)
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
CASR Known Mutation
Calcium Sensing Receptor
Calcium Sensing Receptor
Specimen Type Describes the specimen type needed for testing
Whole Blood EDTA
Specimen Required Defines the optimal specimen. This field describes the type of specimen required to perform the test and the preferred volume to complete testing. The volume allows automated processing, fastest throughput and, when indicated, repeat or reflex testing.
Specimen must arrive within 96 hours of draw.
Container/Tube: Lavender top (EDTA)
Specimen Volume: 3 mL
1. Invert several times to mix blood.
2. Send specimen in original tube.
Additional Information: Transfusions will interfere with testing for up to 4 to 6 weeks. DNA obtained from white cells may not provide useful information for patients who received a recent transfusion of blood that was not leukocyte-reduced. Wait 4 to 6 weeks until transfused cells have left the patient's circulation before drawing the patient's blood specimen for genotype testing.
1. Calcium Sensing Receptor (CASR) Gene Testing Patient Information Sheet (Supply T551) in Special Instructions
2. New York Clients-Informed consent is required. Please document on the request form or electronic order that a copy is on file. An Informed Consent for Genetic Testing (Supply T576) is available in Special Instructions.
Specimen Minimum Volume Defines the amount of specimen required to perform an assay once, including instrument and container dead space. Submitting the minimum specimen volume makes it impossible to repeat the test or perform confirmatory or perform reflex testing. In some situations, a minimum specimen volume may result in a QNS (quantity not sufficient) result, requiring a second specimen to be collected.
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
|Whole Blood EDTA||Refrigerated (preferred)|
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
The extracellular G-protein-coupled calcium sensing receptor (CASR) is an essential component of calcium homeostasis. CASR is expressed at particularly high levels in the parathyroid glands and kidneys. It forms stable homodimeric cell-membrane complexes, which signal upon binding of extracellular calcium ions (Ca[++]). In the parathyroid glands, this 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, renal calcium excretion is upregulated and sodium chloride excretion is downregulated. Ca(++) binding to CASR is highly cooperative within the physiological Ca(++) concentration range, leading to a steep dose-response curve, which results in tight control of serum calcium levels.
To date over 100 different alterations in the CASR gene have been described. Many of these cause diseases of abnormal serum calcium regulation. Inactivating mutations result in undersensing of Ca(++) concentrations and consequent PTH overproduction and secretion. 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 mutations, FHH is due to heterozygous inactivating CASR mutations. Serum calcium levels are mildly-to-moderately elevated. PTH is within the reference range or modestly elevated, phosphate is normal or slightly low, and urinary calcium excretion is low for the degree of hypercalcemia. Unlike patients with primary hyperparathyroidism (PHT), which can be difficult to distinguish from FHH, the majority of FHH patients do not seem to suffer any adverse long-term effects from hypercalcemia and elevated PTH levels. They should therefore generally not undergo parathyroidectomy.
NSPHT is usually due to homozygous or compound heterozygous inactivating CASR mutations, but can occasionally be caused by dominant-negative heterozygous mutations. The condition presents at birth, or shortly thereafter, with severe hypercalcemia requiring urgent parathyroidectomy.
Activating mutations lead to oversensing of Ca(++), resulting in suppression of PTH secretion and consequently hypoparathyroidism. All activating mutations described are functionally dominant and disease inheritance is therefore autosomal dominant. However, sporadic cases also occur. Autosomal dominant hypoparathyroidism may account for many cases of idiopathic hypoparathyroidism. Disease severity depends on the degree of gain of function, spanning the spectrum from mild hypoparathyroidism, which is diagnosed incidentally, to severe and early onset disease. In addition, while the majority of patients suffer only from hypoparathyroidism, a small subgroup with extreme gain of function mutations suffer from concomitant inhibition of renal sodium chloride transport. These individuals may present with additional symptoms of hypokalemic metabolic alkalosis, hyperreninemia, hyperaldosteronism, and hypomagnesemia, consistent with type V Bartter syndrome.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
An interpretive report will be provided
All detected alterations will be evaluated according to American College of Medical Genetics and Genomics (ACMG) recommendations.(1) Variants will be classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
The identification of a disease-causing mutation in an affected family member is necessary before predictive testing for other family members can be offered. If a familial mutation has not been previously identified, order CSRSP/34671 Calcium Sensing Receptor (CASR) Gene, Full Gene Analysis.
Analysis is performed for the familial mutation provided only. This assay does not rule out the presence of other mutations within this gene or within other genes that may be associated with familial hypocalciuric hypercalcemia, neonatal severe primary hyperparathyroidism, or autosomal dominant hypoparathyroidism.
Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Any error in the diagnosis or in the pedigree provided to us, including false-paternity, could lead to an erroneous interpretation of results.
A previous bone marrow transplant from an allogenic donor will interfere with testing. Call Mayo Medical Laboratories for instructions for testing patients who have received a bone marrow transplant.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Richards CS, Bale S, Bellissimo DB, et al: ACMG recommendations for standards for interpretation and reporting of sequence variations: Revisions 2007. Genet Med 2008 Apr;10(4):294-300
2. Hendy GN, D'Souza-Li L, Yang B, et al: Mutations of the calcium-sensing receptor (CASR) in familial hypocalciuric hypercalcemia, neonatal severe hypocalciuric hyperparathyroidism, and autosomal dominant hypocalcemia. Hum Mutat 2000 Oct;16(4):281-296. The authors maintain a CASR polymorphism/mutation database: http://www.casrdb.mcgill.ca/
3. Lienhardt A, Bai M, Lgarde JP, et al: Activating mutations of the calcium-sensing receptor: management of hypocalcemia. J Clin Endocrinol Metab 2001 Nov;86(1):5313-5323
4. Hu J, Spiegel AM: Naturally occurring mutations of the extracellular Ca2+ -sensing receptor: implications for its structure and function. Trends Endocrinol Metab 2003 Aug;14(6):282-288
5. Naesens M, Steels P, Verberckmoes R, et al: Bartter's and Gitelman's syndromes: from gene to clinic. Nephron Physiol 2004;96(3):65-78
6. Egbuna OI, Brown EM: Hypercalcaemic and hypocalcaemic conditions due to calcium-sensing receptor mutations. Best Pract Res Clin Rheumatol 2008;22:129-148
Method Description Describes how the test is performed and provides a method-specific reference
DNA sequencing is utilized to test for the presence of a mutation in the CASR gene that was previously identified in a family member.(Grebe S: Unpublished Mayo method)
Day(s) and Time(s) Test Performed Outlines the days and times the test is performed. This field reflects the day and time the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time required before the test is performed. Some tests are listed as continuously performed, which means assays are performed several times during the day.
Monday; 8 a.m.
Analytic Time Defines the amount of time it takes the laboratory to setup and perform the test. This is defined in number of days. The shortest interval of time expressed is "same day/1 day," which means the results may be available the same day that the sample is received in the testing laboratory. One day means results are available 1 day after the sample is received in the laboratory.
Maximum Laboratory Time Defines the maximum time from specimen receipt at Mayo Medical Laboratories until the release of the test result
Specimen Retention Time Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Whole Blood: 60 days Extracted DNA: indefinitely. Patient must opt out.
Performing Laboratory Location The location of the laboratory that performs the test
CPT Code Information Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Medical Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
81403-Known familial variant
LOINC® Code Information Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the result codes returned for this test or profile.
|Result ID||Reporting Name||LOINC Code|
|34682||Reason For Referral||42349-1|
|34687||Reviewed By||In Process|