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Test Code 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.

Secondary ID

618058

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.

Disease States

  • Autosomal dominant hypoparathyroidism
  • Familial hypocalciuric hypercalcemia
  • Neonatal severe primary hyperparathyroidism
  • Idiopathic hypoparathyroidism

Method Name

Sequence Capture and Next-Generation Sequencing (NGS)

Reporting Name

CASR Full Gene Analysis

Specimen Type

Varies

Specimen Minimum Volume

1 mL

Specimen Stability Information

Specimen Type Temperature Time Special Container
Varies Varies

Reject Due To

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

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.

Day(s) Performed

Varies

Report Available

28 to 42 days

Specimen Retention Time

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

Performing Laboratory

Mayo Clinic Laboratories in Rochester

Test 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