Test Catalog

Test Id : CASRG

CASR Full Gene Sequencing with Deletion/Duplication, Varies

Useful For
Suggests clinical disorders or settings where the test may be helpful

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
Provides information that may help with selection of the correct genetic test or proper submission of the test request

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.

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Name
A short description of the method used to perform the test

Sequence Capture and Next-Generation Sequencing (NGS)

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

CASR Full Gene Analysis

Aliases
Lists additional common names for a test, as an aid in searching

ADH

Autosomal dominant hypocalcemia

Autosomal dominant hypoparathyroidism

Bartter syndrome

Calcium sensing receptor

CASR

FHH

FHH1

Familial hypocalciuric hypercalcemia

Hypercalcemia

Hyperparathyroidism

Hypocalcemia

Hypoparathyroidism

Neonatal hyperparathyroidism

Neonatal severe primary hyperparathyroidism

NextGen Sequencing Test

NHPT

NSPHT

Primary hyperparathyroidism

Specimen Type
Describes the specimen type validated for testing

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 Mutation, 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
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

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

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Forms

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)

-Hereditary Renal Genetic Testing Patient Information (T918)

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

1 mL

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Varies Varies

Useful For
Suggests clinical disorders or settings where the test may be helpful

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
Provides information that may help with selection of the correct genetic test or proper submission of the test request

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.

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 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
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.

Interpretation
Provides information to assist in interpretation of the test results

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.

Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Clinical Correlations:

Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Misinterpretation of results may occur if the information provided is inaccurate or incomplete.

 

If testing was performed because of a clinically significant family history, it is often useful to first test an affected family member. Detection of a reportable variant in an affected family member would allow for more informative testing of at-risk individuals.

 

To discuss the availability of additional testing options or for assistance in the interpretation of these results, contact Mayo Clinic Laboratories genetic counselors at 800-533-1710.

 

Technical Limitations:

Next-generation sequencing may not detect all types of genomic variants. In rare cases, false-negative or false-positive results may occur. The depth of coverage may be variable for some target regions; assay performance below the minimum acceptable criteria or for failed regions will be noted. Given these limitations, negative results do not rule out the diagnosis of a genetic disorder. If a specific clinical disorder is suspected, evaluation by alternative methods can be considered.

 

There may be regions of genes that cannot be effectively evaluated by sequencing or deletion and duplication analysis as a result of technical limitations of the assay, including regions of homology, high guanine-cytosine (GC) content, and repetitive sequences. Confirmation of select reportable variants will be performed by alternate methodologies based on internal laboratory criteria.

 

This test is validated to detect 95% of deletions up to 75 base pairs (bp) and insertions up to 47bp. Deletions-insertions (delins) of 40 or more bp, including mobile element insertions, may be less reliably detected than smaller delins.

 

Deletion/Duplication Analysis:

This analysis targets single and multi-exon deletions/duplications; however, in some instances single exon resolution cannot be achieved due to isolated reduction in sequence coverage or inherent genomic complexity. Balanced structural rearrangements (such as translocations and inversions) may not be detected.

 

This test is not designed to detect low levels of mosaicism or to differentiate between somatic and germline variants. If there is a possibility that any detected variant is somatic, additional testing may be necessary to clarify the significance of results.

 

For detailed information regarding gene specific performance and technical limitations, see Method Description or contact a laboratory Genetic Counselor.

 

If the patient has had an allogeneic hematopoietic stem cell transplant or a recent heterologous blood transfusion, results may be inaccurate due to the presence of donor DNA. Call Mayo Clinic Laboratories for instructions for testing patients who have received a bone marrow transplant.

 

Reclassification of Variants

At this time, it is not standard practice for the laboratory to systematically review previously classified variants on a regular basis. The laboratory encourages health care providers to contact the laboratory at any time to learn how the classification of a particular variant may have changed over time.

 

Variant Evaluation

Evaluation and categorization of variants are performed using published American College of Medical Genetics and Genomics and the Association for Molecular Pathology recommendations as a guideline.(3) Other gene-specific guidelines may also be considered. Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance. Variants classified as benign or likely benign are not reported.

 

Multiple in silico evaluation tools may be used to assist in the interpretation of these results. The accuracy of predictions made by in silico evaluation tools is highly dependent upon the data available for a given gene, and periodic updates to these tools may cause predictions to change over time. Results from in silico evaluation tools are interpreted with caution and professional clinical judgement.

 

Rarely, incidental findings or secondary findings may implicate another predisposition or presence of active disease. Incidental findings may include, but are not limited to, results related to the sex chromosomes. These findings will be carefully reviewed to determine whether they will be reported.

Clinical Reference
Recommendations for in-depth reading of a clinical nature

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

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Description
Describes how the test is performed and provides a method-specific reference

Next-generation sequencing (NGS) and/or Sanger sequencing is performed to test for the presence of variants in coding regions and intron/exon boundaries of the CASR gene, as well as some other regions that have known disease-causing variants. The human genome reference GRCh37/hg19 build was used for sequence read alignment. At least 99% of the bases are covered at a read depth over 30X. Sensitivity is estimated at above 99% for single nucleotide variants, above 94% for deletions-insertions (delins) less than 40 base pairs (bp), above 95% for deletions up to 75 bp and insertions up to 47 bp. NGS and/or a polymerase chain reaction-based quantitative method is performed to test for the presence of deletions and duplications in the CASR gene.

 

There may be regions of the CASR gene that cannot be effectively evaluated by sequencing or deletion and duplication analysis as a result of technical limitations of the assay, including regions of homology, high guanine-cytosine (GC) content, and repetitive sequences.(Unpublished Mayo method)

 

The reference transcript for CASR gene is NM_000388.4. Reference transcript numbers may be updated due to transcript reversioning. Always refer to the final patient report for gene transcript information referenced at the time of testing. Confirmation of select reportable variants may be performed by alternate methodologies based on internal laboratory criteria.

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

Supplemental

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Varies

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

28 to 42 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

Whole blood: 2 weeks (if available); Extracted DNA: 3 months

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their Regional Manager. For assistance, contact Customer Service.

Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.

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 Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

81405

LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.

Test Id Test Order Name Order LOINC Value
CASRG CASR Full Gene Analysis 82534-9
Result Id Test Result Name Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
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 In Process
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

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports

Test Update Resources

Change Type Effective Date
New Test 2022-08-23