Test Catalog

Test Id : PRKSD

PRKAR1A Full Gene Sequencing and Deletion/Duplication Analysis, Varies

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

Aiding in the diagnosis of individuals with suspected Carney complex

 

Aiding in the diagnosis of individuals with suspected acrodysostosis-1 with hormone resistance

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

This test uses Sanger sequencing to evaluate for the presence of PRKAR1A gene variants associated with Carney complex (CNC), acrodysostosis-1 with hormone resistance, or other PRKAR1A-associated conditions. Additionally, quantitative PCR (qPCR) is used to test for the presence of large deletions and duplications of the PRKAR1A gene.

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

Polymerase Chain Reaction (PCR) followed by DNA Sequence Analysis and qPCR

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

PRKAR1A Full Gene Analysis

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

PRKAR1A

Carney

Carney complex

CNC

NAME

LAMB

Myxoma

Cardiac myxoma

Primary pigmented nodular adrenocortical disease

Large-cell calcifying Sertoli cell tumors

LCCSCTs

Acrodysostosis-1 with hormone resistance

Specimen Type
Describes the specimen type validated for testing

Varies

Ordering Guidance

Shipping Instructions

Specimen preferred to arrive within 96 hours of collection.

Necessary Information

1. PRKAR1A-Related Disorders Patient Information (T820) is strongly recommended, but not required, to be filled out and sent with the specimen. This information aids in providing a more thorough interpretation of test results. Ordering providers are strongly encouraged to complete the form and send it with the specimen.

2. Include physician name and phone number with specimen.

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 or a recent (ie, <6 weeks from time of sample collection) heterologous blood transfusion will interfere with testing. Call 800-533-1710 for instructions for testing patients who have received a bone marrow transplant.

 

Submit only 1 of the following specimens:

 

Specimen Type: Whole blood

Container/Tube: Lavender top (EDTA)

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send specimen in original tube. Do not aliquot.

Specimen Stability Information: Ambient (preferred) 4 days/Refrigerated 14 days

 

Specimen Type: Extracted DNA

Container/Tube: 2 mL screw top tube

Specimen Volume: 100 mcL (microliters)

Collection Instructions:

1. The preferred volume is 100 mcL at a concentration of 250 ng/mcL.

2. Include concentration and volume on tube.

Specimen Stability Information: Frozen (preferred)/Ambient/Refrigerated

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

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 in Special Instructions:

-Informed Consent for Genetic Testing (T576)

-Informed Consent for Genetic Testing-Spanish (T826)

2. PRKAR1A-Related Disorders Patient Information (T820) is recommended. See Special Instructions.

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

Blood: 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

Aiding in the diagnosis of individuals with suspected Carney complex

 

Aiding in the diagnosis of individuals with suspected acrodysostosis-1 with hormone resistance

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

This test uses Sanger sequencing to evaluate for the presence of PRKAR1A gene variants associated with Carney complex (CNC), acrodysostosis-1 with hormone resistance, or other PRKAR1A-associated conditions. Additionally, quantitative PCR (qPCR) is used to test for the presence of large deletions and duplications of the PRKAR1A gene.

Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Carney complex (CNC) is an autosomal dominant disorder caused by heterozygous germline pathogenic inactivating variants in the PRKAR1A gene. This condition has also been designated by the following acronyms: NAME (nevi, atrial myxomas, ephelides) and LAMB (lentigines, atrial myxoma, blue nevi). CNC is characterized by skin pigmentary abnormalities, myxomas, endocrine tumors, and schwannomas. The most common presenting feature of CNC is unusual skin pigmentation, including brown skin spots called lentigines or blue-black moles called blue nevi. Myxomas are noncancerous (benign) tumors which can occur in the heart (cardiac myxoma), skin, breast, and other internal organs. Cardiac myxomas can occur at a young age, and may block blood flow through the heart, causing serious complications or sudden death. Approximately 25% of affected individuals will develop primary pigmented nodular adrenocortical disease (PPNAD), which can lead to development of Cushing syndrome. Large-cell calcifying Sertoli cell tumors occur in most affected males and may develop in the first decade of life in about one third of cases. Multiple thyroid nodules are present in as many as 75% of affected individuals. Pituitary adenomas resulting in clinically evident acromegaly occur in approximately 10% of adults with CNC. Another 10% of affected individuals have psammomatous melanotic schwannomas, which are typically benign but may be malignant.

 

PRKAR1A encodes for cAMP-dependent protein kinase type I-alpha regulatory subunit. PRKAR1A functions as a canonical tumor-suppressor gene, with biallelic inactivation in tumors resulting in constitutive activation of protein kinase A. Approximately 70% of individuals with a diagnosis of CNC have an affected parent, while approximately 30% have a de novo pathogenic variant. CNC is a highly penetrant disorder, with approximately 95% of those with a pathogenic PRKAR1A variant developing disease by age 50 years. The proportion of probands with a pathogenic variant detectable by sequence analysis is approximately 60% but can be higher (approximately 80%) in individuals presenting with Cushing syndrome caused by PPNAD. Approximately 10% to 20% of individuals with CNC who test negative for a pathogenic sequence variant may have a large PRKAR1A deletion.

 

While the majority of reported pathogenic PRKAR1A gene variants are associated with CNC, this gene is also associated with an autosomal dominant condition called acrodysostosis-1 with hormone resistance. This condition is characterized by multiple hormone resistance, short stature, brachycephaly, and short broad hands with short metacarpals and phalanges, among other features. This phenotype results from pathogenic PRKAR1A variants in 1 of the 2 cAMP-binding domains and has a different mechanism of disease than CNC.

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

Evaluation and categorization of variants is performed using the most recent published American College of Medical Genetics and Genomics (ACMG) recommendations as a guideline. Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.

 

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 predictions made by these tools may change over time. Results from in silico evaluation tools should be interpreted with caution and professional clinical judgment.

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

Clinical Correlations:

Some individuals may have a PRKAR1A variant that is not identified by the methods performed (eg, promoter variants, deep intronic variants). The absence of a variant, therefore, does not eliminate the possibility of disease. Genomic regions that are not sufficiently covered for analysis and interpretation will be indicated on the laboratory report.

 

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

 

For predictive testing of asymptomatic individuals, it is often useful to first test an affected family member.

 

Identification of a pathogenic variant in an affected individual allows for more informative testing of at-risk individuals.

 

Technical Limitations:

If the patient has had an allogeneic blood or bone marrow transplant or a recent (ie, <6 weeks from time of sample collection) heterologous blood transfusion, results may be inaccurate due to the presence of donor DNA. Call 800-533-1710 for instructions for testing patients who have received a bone marrow transplant.

 

Reclassification of Variants Policy:

At this time, it is not standard practice for the laboratory to systematically review likely pathogenic variants or variants of uncertain significance that have been detected and reported. The laboratory encourages health care providers to contact the laboratory at any time to learn how the status of a particular variant may have changed over time. Consultation with a genetics professional should be considered for interpretation of this result.

 

A list of benign and likely benign variants detected for this patient is available from the laboratory upon request.

 

Contact the laboratory if additional information is required regarding the transcript or human genome assembly used for the analysis of this patient's results.

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

1. Maleszewski JJ, Larsen BT, Kip NS, et al: PRKAR1A in the development of cardiac myxoma. Am J Surg Pathol 2014;38:1079-1087

2. Rhayem Y, Le Stunff C, Abdel Khalek W, et al: Functional characterization of PRKAR1A mutations reveals a unique molecular mechanism causing acrodysostosis but multiple mechanisms causing Carney complex. J Biol Chem. 2015;290(46):27816-27828

3. Salpea P, Horvath A, London E, et al: Deletions of the PRKAR1A locus at 17q24.2-q24.3 in Carney complex: genotype-phenotype correlations and implications for genetic testing. J Clin Endocrinol Metab. 2014;99(1):E183-188

4. Stratakis CA, Raygada M: Carney complex. In: Adam MP, Ardinger HH, Pagon RA, et al. GeneReviews [Internet]. University of Washington, Seattle;2003. Updated August 16, 2018 Accessed September 22, 2021. Available at www.ncbi.nlm.nih.gov/books/NBK1286/

5. OMIM. Carney complex. Johns Hopkins University; Accessed September 22, 2021. Available at www.ncbi.nlm.nih.gov/omim/?term=carney+complex

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

Polymerase chain reaction (PCR) followed by bidirectional DNA sequence analysis is performed to test for the presence of sequence variants in all coding regions and intron/exon boundaries of the PRKAR1A gene. Quantitative PCR (qPCR) using SYBR green fluorescent-dye terminator chemistry is performed to test for the presence of whole exon deletions and duplications.(Unpublished Mayo method)

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

No

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.

3 to 7 days

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

Extracted DNA:2 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.

81479

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
PRKSD PRKAR1A Full Gene Analysis 94214-4
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.
605940 Result Summary 50397-9
605941 Result Details 82939-0
605942 Interpretation 69047-9
605943 Additional Information 48767-8
605944 Method 85069-3
605945 Disclaimer 62364-5
605946 Reviewed 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