Test Catalog

Test Id : EDSGP

Ehlers-Danlos Syndrome Panel (12 Genes), Next-Generation Sequencing and Deletion/Duplication Analysis, Varies

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

Confirmation of a clinical diagnosis of Ehlers-Danlos Syndrome (EDS)

 

Differentiating between the different subtypes of EDS for diagnosis and management purposes

 

Ascertaining carrier status of family members of individuals diagnosed with EDS for genetic counseling purposes

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

This test includes next-generation sequencing with deletion/duplication (copy number variation) analysis and supplemental Sanger sequencing to evaluate for variants in the ADAMTS2, ATP7A, CHST14, COL1A1, COL1A2, COL3A1, COL5A1, COL5A2, FKBP14, FLNA, PLOD1, and SLC39A13 genes.

 

Identification of a pathogenic variant may assist with prognosis, clinical management, familial screening, and genetic counseling.

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

Custom Sequence Capture and Targeted Next-Generation Sequencing followed by Polymerase Chain Reaction (PCR) and Supplemental Sanger Sequencing or qPCR if needed

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

Ehlers-Danlos Syndrome Gene Panel

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

ADAMTS2

ATP7A

CHST14

COL1A1

COL1A2

COL3A1

COL5A1

COL5A2

Ehlers Danlos Syndrome (EDS)

FKBP14

PLOD1

SLC39A13

Classical EDS (cEDS)

Vascular EDS (vEDS)

Dermatosparaxis EDS (dEDS)

Musculocontractural EDS (mcEDS)

Arthrochalasia EDS (aEDS)

Cardiac-valvular EDS (cvEDS)

Kyphoscoliotic EDS (kEDS)

Spondylodysplastic EDS (spEDS)

EDS Type I

EDS Type II

EDS Type IV

EDS Type VIIC

Occipital horn syndrome

EDS Type IX

Periventricular nodular heterotopia

Filamin A

Next Gen Sequencing Test

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

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.

 

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:

-Informed Consent for Genetic Testing (T576)

-Informed Consent for Genetic Testing (Spanish) (T826)

2. Marfan and Related Disorders Patient Information (T636) is recommended

3. If not ordering electronically, complete, print, and send a Cardiovascular Test Request Form (T724) with the specimen.

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

Whole 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

Confirmation of a clinical diagnosis of Ehlers-Danlos Syndrome (EDS)

 

Differentiating between the different subtypes of EDS for diagnosis and management purposes

 

Ascertaining carrier status of family members of individuals diagnosed with EDS for genetic counseling purposes

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

This test includes next-generation sequencing with deletion/duplication (copy number variation) analysis and supplemental Sanger sequencing to evaluate for variants in the ADAMTS2, ATP7A, CHST14, COL1A1, COL1A2, COL3A1, COL5A1, COL5A2, FKBP14, FLNA, PLOD1, and SLC39A13 genes.

 

Identification of a pathogenic variant may assist with prognosis, clinical management, familial screening, and genetic counseling.

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

The Ehlers Danlos syndromes (EDS) are a clinically and genetically diverse group of heritable connective tissue disorders. An EDS classification system proposed by the International EDS Consortium identifies 13 subtypes of EDS, with an overall estimated prevalence of EDS between 1:5000 and 1:25,000. Over 90% of cases are either classic or hypermobile EDS (cEDS or hEDS), while less than 5% of cases are vascular EDS (vEDS). Other, rarer, subtypes of EDS also exist and are listed in the table below.

 

The clinical hallmarks of EDS are joint hypermobility, skin hyperextensibility, and tissue fragility. However, a variety of skin, ligament, joint, and cardiovascular features are seen across the spectrum of EDS. A clinical diagnosis of a specific subtype of EDS may be suspected based on a combination of major (a symptom present in the majority of affected individuals) and minor (a symptom of lesser diagnostic specificity that supports the diagnosis) clinical criteria. However, due to the clinical overlap between EDS subtypes and other heritable connective tissue disorders (eg, Marfan syndrome and Loeys-Dietz syndrome), a definitive diagnosis of all EDS subtypes (except EDS hypermobility type) relies on the identification of a causative variant in the appropriate gene.

 

Genetic variants in collagen-encoding or collagen-modifying genes have been identified as the cause of EDS in the majority of subtypes. These variants result in defects in collagen structure, processing, folding, and cross-linking. One notable exception to this is hypermobile EDS (hEDS). Hypermobile EDS is inherited in an autosomal dominant inheritance pattern, similar to cEDS and vEDS, however, the molecular basis of this condition is unknown, and a diagnosis is based on clinical criteria.

 

This panel also tests for variants in the ATP7A and FLNA genes, which result in X-linked conditions. Some patients with these conditions have clinical overlap with EDS.

 

Table1. Genes included in this gene panel

Gene symbol

Protein

Inheritance*

EDS Cclassification

ADAMTS2

Procollagen I N-proteinase (NPI)

AR

Dermatosparaxis EDS (dEDS) / human dermatosparaxis EDS VIIC

ATP7A

Copper-transporting ATPase 1

XL

Occipital horn syndrome

CHST14

Dermatan-4-sulfotransferase-1 (D4ST1)

AR

Musculocontractural EDS (mcEDS-CHST14)

COL1A1

Collagen alpha-1(I) chain

AD

AD

AD

Classical EDS (cEDS)

Vascular EDS (vEDS)

Arthrochalasia EDS (aEDS)

COL1A2

Collagen alpha-2(I) chain

AD

AR

Arthrochalasia EDS (aEDS)

Cardiac valvular EDS (cvEDS)

COL3A1

Collagen alpha-1(III) chain

AD

Vascular EDS (vEDS)

COL5A1

Collagen alpha-1(V) chain

AD

Classical EDS (cEDS)

COL5A2

Collagen alpha-2(V) chain

AD

Classical EDS (cEDS)

FKBP14

Peptidyl-prolyl cis-trans isomerase FKBP14 (FK506 binding protein 14)

AR

Kyphoscoliotic EDS (kEDS-FKBP14)

FLNA

Filamin A

XL

Filamin A related EDS with periventricular nodular heterotopia

PLOD1

Procollagen-lysine 5-dioxygenase

 

AR

Kyphoscoliotic EDS (kEDS – PLOD1)

SLC39A13

Zinc transporter ZIP13

AR

Spondylodysplastic EDS (spEDS-SLC39A13)

 

*Abbreviations: Autosomal dominant (AD), autosomal recessive (AR), X-linked (XL), Ehlers-Danlos syndrome (EDS)

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.(1) 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 who have involvement of 1 or more of the genes on the panel may have a variation 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.

 

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:

Next-generation sequencing (NGS) may not detect all types of genetic variants. Additionally, rare alteration (ie, polymorphisms) may be present that could lead to false negative or positive results. If results do not match clinical findings, consider alternative methods for analyzing these genes, such as Sanger sequencing.

 

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 are 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 the patient's results.

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

1. 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

2. Malfait F, Francomano C, Byers P, et al: The 2017 international classification of the Ehlers-Danlos syndromes. Am J Med Genet C Semin Med Genet. 2017;175(1):8-26. doi: 10.1002/ajmg.c.31552

3. Meester JAN, Verstraeten A, Schepers D, et al: Differences in manifestations of Marfan syndrome, Ehlers-Danlos syndrome, and Loeys-Dietz syndrome. Ann Cardiothorac Surg. 2017;6(6):582-594. doi: 10.21037/acs.2017.11.03

4. Brady AF, Demirdas S, Fournel-Gigleux S, et al: The Ehlers-Danlos syndromes, rare types. Am J Med Genet C Semin Med Genet. 2017;175(1):70-115. doi: 10.1002/ajmg.c.31550

5. Bowen JM, Sobey GJ, Burrows NP, et al: Ehlers-Danlos syndrome, classical type. Am J Med Genet C Semin Med Genet. 2017;175(1):27-39. doi: 10.1002/ajmg.c.31548

6. Bursztejn AC, Baumann M, Lipsker D: Ehlers-Danlos syndrome related to FKBP14 mutations: detailed cutaneous phenotype. Clin Exp Dermatol 2017;42(1):64-67. doi: 10.1111/ced.12983

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) is performed using an Illumina instrument with paired-end reads. The DNA is prepared for NGS using a custom Agilent SureSelect Target Enrichment System. Data is analyzed with a bioinformatics software pipeline for sequence variants and the presence of large intragenic deletions and duplications. Supplemental Sanger sequencing or qPCR may be performed occasionally in regions where NGS is insufficient for data capture or not specific enough to correctly identify a variant. Sanger sequencing or qPCR may also be used for confirmatory testing.(Unpublished Mayo method)

 

Genes analyzed: ADAMTS2, ATP7A, CHST14, COL1A1, COL1A2, COL3A1, COL5A1, COL5A2, FKBP14, FLNA, PLOD1, SLC39A13

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.

Monday

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.

2 to 4 weeks

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

81408 x 2

81479 (if appropriate for government payers)

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
EDSGP Ehlers-Danlos Syndrome Gene Panel 93200-4
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.
601731 Gene(s) Evaluated 48018-6
601732 Result Summary 47997-2
601733 Result Details 82939-0
601734 Interpretation 69047-9
601735 Additional Information 48767-8
601736 Method 85069-3
601737 Disclaimer 62364-5
601738 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

Test Update Resources

Change Type Effective Date
Obsolete Test 2022-12-15