Test Catalog

Test Id : CAORG

Comprehensive Marfan, Loeys-Dietz, Ehlers-Danlos, and Aortopathy Gene Panel, Varies

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

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 and copy number variants in 48 genes associated with Marfan syndrome, Loeys-Dietz syndrome, Ehlers-Danlos syndrome, heritable thoracic aortic disease/aortopathy and related conditions with overlapping clinical presentation: ACTA2, ADAMTS10, ADAMTS17, ADAMTS2, AEBP1, ATP7A, B3GALT6, B3GAT3, B4GALT7, BGN, CBS, CHST14, COL12A1, COL1A1, COL1A2, COL3A1, COL5A1, COL5A2, DSE, EFEMP2, FBN1, FBN2, FKBP14, FLNA, LOX, LTBP3, MED12, MFAP5, MYH11, MYLK, NOTCH1, PLOD1, PRDM5, PRKG1, SKI, SLC2A10, SLC39A13, SMAD2, SMAD3, SMAD4, SMAD6, SPARC, TGFB2, TGFB3, TGFBR1, TGFBR2, TNXB, and ZNF469. See Targeted Genes and Methodology Details for Comprehensive Marfan, Loeys-Dietz, Ehlers-Danlos, and Aortopathy Gene Panel and Method Description for additional details.

 

Identification of a disease-causing variant may assist with diagnosis, prognosis, clinical management, familial screening, and genetic counseling for Marfan syndrome, Loeys-Dietz syndrome, Ehlers-Danlos syndrome, and hereditary aortopathies.

 

Prior Authorization is available for this assay.

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 Targeted Next-Generation Sequencing followed by Polymerase Chain Reaction (PCR) and Sanger Sequencing.

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

Comprehensive Aortopathy Gene Panel

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

Aortic aneurysm

Aortic dissection

Aortopathy

Arterial tortuosity syndrome

Brittle cornea syndrome

Congenital contractural arachnodactyly

Cutis laxa

EDS

Ehlers-Danlos syndrome, classic type

Ehlers-Danlos syndrome, kyphoscoliotic type

Ehlers-Danlos syndrome, musculocontractural type

Ehlers-Danlos syndrome, myopathic type

Ehlers-Danlos syndrome, spondylodysplastic type

Ehlers-Danlos syndrome, vascular type

Familial Thoracic Aortic Aneurysm/Dissection

FTAAD

Heritable thoracic aortic disease

Homocystinuria

LDS

Loeys-Dietz syndrome

Marfan syndrome

Meester-Loeys syndrome

Menkes disease

MFS

NextGen Sequencing Test

Periventricular nodular heterotopia

Shprintzen-Goldberg syndrome

Spondyloepimetaphyseal dysplasia, X-linked

Weill-Marchesani syndrome

Specimen Type
Describes the specimen type validated for testing

Varies

Ordering Guidance

Customization of this panel and single gene analysis for any gene present on this panel are available. For more information see CGPH / Custom Gene Panel, Hereditary, Next-Generation Sequencing, Varies.

 

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.

Shipping Instructions

Specimen preferred to arrive within 96 hours of collection.

Necessary Information

Prior Authorization is available for this test. Submit the required form with the 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 will interfere with testing. Call 800-533-1710 for instructions for testing patients who have received a bone marrow transplant.

 

Specimen Type: Whole blood

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

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. Connective Tissue/Cerebrovascular Disease Genetic Testing Patient Information

3. Cardiomyopathy Aortopathy Gene Panel (CAORG) Prior Authorization Ordering Instructions

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

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 and copy number variants in 48 genes associated with Marfan syndrome, Loeys-Dietz syndrome, Ehlers-Danlos syndrome, heritable thoracic aortic disease/aortopathy and related conditions with overlapping clinical presentation: ACTA2, ADAMTS10, ADAMTS17, ADAMTS2, AEBP1, ATP7A, B3GALT6, B3GAT3, B4GALT7, BGN, CBS, CHST14, COL12A1, COL1A1, COL1A2, COL3A1, COL5A1, COL5A2, DSE, EFEMP2, FBN1, FBN2, FKBP14, FLNA, LOX, LTBP3, MED12, MFAP5, MYH11, MYLK, NOTCH1, PLOD1, PRDM5, PRKG1, SKI, SLC2A10, SLC39A13, SMAD2, SMAD3, SMAD4, SMAD6, SPARC, TGFB2, TGFB3, TGFBR1, TGFBR2, TNXB, and ZNF469. See Targeted Genes and Methodology Details for Comprehensive Marfan, Loeys-Dietz, Ehlers-Danlos, and Aortopathy Gene Panel and Method Description for additional details.

 

Identification of a disease-causing variant may assist with diagnosis, prognosis, clinical management, familial screening, and genetic counseling for Marfan syndrome, Loeys-Dietz syndrome, Ehlers-Danlos syndrome, and hereditary aortopathies.

 

Prior Authorization is available for this assay.

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

Inherited forms of aortic disease, or aortopathies, may be associated with isolated thoracic aortic aneurysms and dissections or conditions with multi-system involvement. This gene panel includes genes for multiple conditions that may have aortopathy as a feature, including Marfan syndrome, Loeys-Dietz syndrome, Ehlers-Danlos syndrome, arterial tortuosity syndrome, and heritable thoracic aortic disease (also known as familial thoracic aortic aneurysm/dissection: FTAAD). Other heritable conditions with overlapping clinical presentations are also covered by this panel. Confirming a genetic diagnosis in the setting of aortopathy may aid in differentiating the genetic etiology of complex or ambiguous clinical presentations, treatment decisions, and genetic counseling.

 

Marfan syndrome (MFS) is an autosomal dominant genetic disorder affecting the connective tissue that occurs in approximately 1 to 2 per 10,000 individuals. It is characterized by the presence of skeletal, ocular, and cardiovascular manifestations and is caused by variants in the FBN1 gene. Skeletal findings may include tall stature, chest wall deformity, scoliosis, and joint hypermobility. Lens dislocation (ectopia lentis) is the cardinal ocular feature with mitral valve prolapse and aortic root dilatation/dissection the main cardiovascular features.(1)

 

Loeys-Dietz syndrome (LDS) is an autosomal dominant connective tissue disease with significant overlap with Marfan syndrome but may include involvement of other organ systems and is primarily caused by variants in TGFBR1 and TGFBR2.(2,3) Features of LDS that are not typical of MFS include craniofacial and neurodevelopmental abnormalities and arterial tortuosity with increased risk for aneurysm and dissection throughout the arterial tree. Variants in the SMAD3 gene have been reported in families with an LDS-like phenotype with arterial aneurysms and tortuosity and early onset osteoarthritis. Variants in the TGFB3 gene have also been reported in families with an LDS-like phenotype, although these individuals tended to not have arterial tortuosity.

 

Heritable thoracic aortic disease (FTAAD) is a genetic condition primarily involving dilatation and dissection of the thoracic aorta but may also include aneurysm and dissection of other arteries. This condition has a highly variable age of onset and presentation and may involve additional features such as congenital heart defects and other features of connective tissue disease or smooth muscle abnormalities depending on the causative gene. The gene most commonly involved in FTAAD is ACTA2.(4,5)

 

Vascular Ehlers-Danlos syndrome (also known as vEDS or EDS IV) is an autosomal dominant connective tissue disease caused by variants in the COL3A1 gene. vEDS may present with characteristic facial features, thin, translucent skin, easy bruising, and arterial, intestinal, and uterine fragility. Arterial rupture may be preceded by aneurysm or dissection or may occur spontaneously.(6) Classic Ehlers-Danlos syndrome types I and II (also known as cEDS) are caused by variants in the COL5A1 and COL5A2 genes. Aortic root dilation and, more rarely, spontaneous vessel rupture have been reported in cEDS.(7)

 

Other genes included on this panel cause conditions with clinical overlap with those above. Examples include genes associated with rare, autosomal recessive forms of Ehlers-Danlos syndrome, the FLNA gene associated with periventricular nodular heterotopia, the FBN2 gene associated with congenital contractural arachnodactyly, the CBS gene associated with homocystinuria, the SLC2A10 gene associated with autosomal recessive arterial tortuosity syndrome, and the NOTCH1 gene associated with aortic valve disease and severe valve calcification. Currently, expert consensus indicates NOTCH1 variants may be predictive of thoracic aortic enlargement without evidence of progression to aortic dissection.(8-12)

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.(13) 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 the 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 47 bp. 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.

 

Genes may be added or removed based on updated clinical relevance. Refer to the Targeted Genes and Methodology Details for Comprehensive Marfan, Loeys-Dietz, Ehlers-Danlos, and Aortopathy Gene Panel for the most up to date list of genes included in this test. 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 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 healthcare 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 is performed using published American College of Medical Genetics and Genomics and the Association for Molecular Pathology recommendations as a guideline.(13) 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 should be interpreted with caution and professional clinical judgment.

 

Rarely, incidental 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. Loeys BL, Dietz HC, Braverman AC, et al: The revised Ghent nosology for the Marfan syndrome. J Med Genet. 2010 Jul;47(7):476-485

2. Loeys BL, Schwarze U, Holm T, et al: Aneurysm syndromes caused by mutations in the TGF-beta receptor. N Engl J Med. 2006 Aug 24;355(8):788-798

3. Loeys BL, Chen J, Neptune ER, et al: A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or TGFBR2. Nat Genet. 2005 Mar;37(3):275-281

4. Milewicz DM, Regalado E: Heritable thoracic aortic disease overview. In: Adam MP, Ardinger HH, Pagon RA, et al, eds. GeneReviews [Internet]. University of Washington, Seattle; 2003. Updated December 14, 2017. Accessed September 22, 2021. Available at www.ncbi.nlm.nih.gov/books/NBK1120/

5. Guo DC, Pannu H, Tran-Fadulu V, et al: Mutations in smooth muscle a-actin (ACTA2) lead to thoracic aortic aneurysms and dissections. Nat Genet. 2007 Dec;39(12):1488-1493

6. Pepin M, Schwarze U, Superti-Furga A, Byers PH: Clinical and genetic features of Ehlers-Danlos syndrome type IV, The vascular type. N Engl J Med. 2000 Mar 9;342(10):673-680

7. Malfait F, Wenstrup R, Paepe AD: Classic Ehlers-Danlos syndrome. In: Adam MP, Ardinger HH, Pagon RA, et al, eds. GeneReviews [Internet]. University of Washington, Seattle; 2007. Updated July 26, 2018. Accessed September 22, 2021. Available at www.ncbi.nlm.nih.gov/books/NBK1244/

8. Chen MH, Walsh CA: FLNA-related periventricular nodular heterotopia. In: Adam MP, Ardinger HH, Pagon RA, et al, eds. GeneReviews [Internet]. University of Washington, Seattle; 2002. Updated September 17, 2015. Accessed September 22, 2021. Available at www.ncbi.nlm.nih.gov/books/NBK1213/

9. Callewaert B. Congenital contractural arachnodactyly. In: Adam MP, Ardinger HH, Pagon RA, et al, eds. GeneReviews [Internet]. University of Washington, Seattle; 2003. Updated October 21, 2019. Accessed September 30, 2021. Available at www.ncbi.nlm.nih.gov/books/NBK1386/

10. Sacharow SJ, Picker JD, Levy HL: Homocystinuria caused by cystathionine beta-synthase deficiency. In: Adam MP, Ardinger HH, Pagon RA, et al, eds. GeneReviews [Internet]. University of Washington, Seattle; 2003. Updated May 18, 2017. Accessed September 30, 2021. Available at www.ncbi.nlm.nih.gov/books/NBK1524/

11. Coucke PJ, Willaert A, Wessels MW, et al: Mutations in the facilitative glucose transporter GLUT10 alter angiogenesis and cause arterial tortuosity syndrome. Nat Genet. 2006 Apr;38(4):452-457

12. Clinical Genome Resource: Gene-Disease Validity Classification Summary for NOTCH1-familial thoracic aortic aneurysm and aortic dissection. ClinGen; 2016. Accessed July 14, 2022. Available at https://search.clinicalgenome.org/kb/gene-validity/CGGCIEX:assertion_8269

13. 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 genes analyzed, 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 genes analyzed.

 

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. See Targeted Genes and Methodology Details for Comprehensive Marfan, Loeys-Dietz, Ehlers-Danlos, and Aortopathy Gene Panel for details regarding the targeted genes analyzed for each test and specific gene regions not routinely covered.(Unpublished Mayo method)

Confirmation of select reportable variants may be performed by alternate methodologies based on internal laboratory criteria.

 

Genes analyzed: ACTA2, ADAMTS10, ADAMTS17, ADAMTS2, AEBP1, ATP7A, B3GALT6, B3GAT3, B4GALT7, BGN, CBS, CHST14, COL12A1, COL1A1, COL1A2, COL3A1, COL5A1, COL5A2, DSE, EFEMP2, FBN1, FBN2, FKBP14, FLNA, LOX, LTBP3, MED12, MFAP5, MYH11, MYLK, NOTCH1, PLOD1, PRDM5, PRKG1, SKI, SLC2A10, SLC39A13, SMAD2, SMAD3, SMAD4, SMAD6, SPARC, TGFB2, TGFB3, TGFBR1, TGFBR2, TNXB, and ZNF469

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

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.

81410

Prior Authorization
Prior Authorization may be required by your insurance carrier.

Insurance preauthorization is available for this testing; forms are available.

 

Patient financial assistance may be available to those who qualify. Patients who receive a bill from Mayo Clinic Laboratories will receive information on eligibility and how to apply.

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
CAORG Comprehensive Aortopathy Gene Panel 51966-0
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.
617156 Test Description 62364-5
617157 Specimen 31208-2
617158 Source 31208-2
617159 Result Summary 50397-9
617160 Result 82939-0
617161 Interpretation 69047-9
617162 Additional Results In Process
617163 Resources 99622-3
617164 Additional Information 48767-8
617165 Method 85069-3
617166 Genes Analyzed 48018-6
617167 Disclaimer 62364-5
617168 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 2022-12-15