Test Code NHEM Hereditary Erythrocytosis Focused Gene Panel, Next-Generation Sequencing, Varies
Ordering Guidance
Polycythemia vera and acquired causes of erythrocytosis should be excluded before ordering this evaluation.
For a complete evaluation including hemoglobin electrophoresis testing and hereditary erythrocytosis variant analysis of the most common gene regions associated with hereditary erythrocytosis in an algorithmic fashion, order REVE2 / Erythrocytosis Evaluation, Blood. See Erythrocytosis Genotyping Comparison Chart for a comparison of erythrocytosis testing options.
The hemoglobin genes, HBA1/HBA2 and HBB, are not interrogated in this assay.
Multiple gene panels are available. For more information see NHEP and Subpanel Comparison Gene List.
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 variants 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.
Shipping Instructions
Specimen preferred to arrive within 96 hours of collection.
Necessary Information
1. Erythrocytosis Patient Information is required. Testing may proceed without the patient information, however, the information aids in providing a more thorough interpretation. Ordering providers are strongly encouraged to fill out the form and send with the specimen.
2. If form not provided, include the following information with the test request: clinical diagnosis, pertinent clinical history (ie, complete blood cell count results and relevant clinical notes), and differentials based on clinical presentation and/or laboratory findings.
Specimen Required
Submit only 1 of the following specimens:
Specimen Type: Whole blood
Patient Preparation: A previous bone marrow transplant from an allogenic donor will interfere with whole blood testing. Call 800-533-1710 for instructions for testing patients who have received a bone marrow transplant.
Container/Tube:
Preferred: Lavender top (EDTA)
Acceptable: Yellow top (ACD)
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) 4 days/Refrigerated
Specimen Type: Skin biopsy
Supplies: Fibroblast Biopsy Transport Media (T115)
Container/Tube: Sterile container with any standard cell culture media (eg, minimal essential media, RPMI 1640). The solution should be supplemented with 1% penicillin and streptomycin.
Specimen Volume: 4-mm punch
Specimen Stability Information: Refrigerated (preferred)/Ambient
Additional Information: A separate culture charge will be assessed under CULFB / Fibroblast Culture for Biochemical or Molecular Testing. An additional 3 to 4 weeks is required to culture fibroblasts before genetic testing can occur.
Specimen Type: Cultured fibroblast
Container/Tube: T-25 flask
Specimen Volume: 2 Flasks
Collection Instructions: Submit confluent cultured fibroblast cells from a skin biopsy from another laboratory. Cultured cells from a prenatal specimen will not be accepted.
Specimen Stability Information: Ambient (preferred)/Refrigerated (<24 hours)
Additional Information: A separate culture charge will be assessed under CULFB / Fibroblast Culture for Biochemical or Molecular Testing. An additional 3 to 4 weeks is required to culture fibroblasts before genetic testing can occur.
Forms
1. Erythrocytosis Patient Information (T694) is required.
2. 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)
3. If not ordering electronically, complete, print, and send a Benign Hematology Test Request (T755) with the specimen.
Secondary ID
618991Useful For
Focused evaluation of an individual with JAK2-V617F negative erythrocytosis associated with lifelong sustained increased red blood cell (RBC) mass, hemoglobin, or hematocrit
Providing a focused genetic evaluation for patients with a personal or family history suggestive of hereditary erythrocytosis
Establishing a diagnosis of a hereditary erythrocytosis or related disorder, allowing for appropriate management and surveillance of disease features based on the gene involved
Testing Algorithm
This evaluation is recommended for patients presenting with lifelong elevation in hemoglobin or hematocrit, usually with a positive family history of similar symptoms. Polycythemia vera should be excluded prior to testing as it is much more common than hereditary erythrocytosis and can be present even in young patients. A JAK2 V617F or JAK2 exon 12 variant should not be present. More sensitive variant-specific test for JAK2 V617F is highly recommended prior to ordering this test. Additionally, alpha and beta chain high-oxygen affinity hemoglobin variants should be excluded prior to ordering this test panel.
If skin biopsy (fresh) is received, fibroblast culture will be added at an additional charge. If viable cells are not obtained, the client will be notified.
Special Instructions
Method Name
Sequence Capture and Targeted Next-Generation Sequencing (NGS) followed by Polymerase Chain Reaction (PCR) and Sanger Sequencing.
Specimen Type
VariesSpecimen 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.Reference Values
An interpretive report will be provided.
Interpretation
All detected variants are evaluated according to American College of Medical Genetics and Genomics recommendations.(1) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.
Method Description
Next-generation sequencing (NGS) and/or Sanger sequencing are 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.(Unpublished Mayo method)
See Targeted Genes and Methodology Details for Hereditary Erythrocytosis Focused Gene Panel for details regarding the targeted genes analyzed for each test and specific gene regions not routinely covered.
Reference transcript numbers may be updated due to transcript re-versioning. 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.
Genes analyzed: BPGM, EGLN1, EPAS1, EPOR, and VHL
Day(s) Performed
Varies
Report Available
28 to 42 daysSpecimen Retention Time
Whole blood: 2 weeks (if available); Extracted DNA: 3 monthsPerforming Laboratory
Mayo Clinic Laboratories in RochesterCPT Code Information
81404
81479
81479 (if appropriate for government payers)
LOINC Code Information
Test ID | Test Order Name | Order LOINC Value |
---|---|---|
NHEM | Erythrocytosis Focused Panel, NGS | 103736-5 |
Result ID | Test Result Name | Result LOINC Value |
---|---|---|
618992 | Test Description | 62364-5 |
618993 | Specimen | 31208-2 |
618994 | Source | 31208-2 |
618995 | Result Summary | 50397-9 |
618996 | Result | 82939-0 |
618997 | Interpretation | 59465-5 |
618998 | Additional Results | 82939-0 |
618999 | Resources | 99622-3 |
619000 | Additional Information | 48767-8 |
619001 | Method | 85069-3 |
619002 | Genes Analyzed | 82939-0 |
619003 | Disclaimer | 62364-5 |
619004 | Released By | 18771-6 |
Reflex Tests
Test ID | Reporting Name | Available Separately | Always Performed |
---|---|---|---|
CULFB | Fibroblast Culture for Genetic Test | Yes | No |