Test Code BMFGP Inherited Bone Marrow Failure Gene Panel, Varies
Ordering Guidance
Patients who have had a previous bone marrow transplant from an allogenic donor should not have testing performed on blood, bone marrow, or saliva because any results generated will reflect the genome of the donor rather than the recipient. Testing on patients who have an active hematologic malignancy or hematologic disorder with clonal proliferation may identify both somatic mutations and germline variants, which may result in test failure or necessitate follow-up testing to determine whether the detected variant is germline or somatic. For these patients, testing a skin biopsy or cultured fibroblasts is recommended. For instructions for testing patients who have received a bone marrow transplant or have an active hematologic disorder, call 800-533-1710. For more information see Cautions.
Customization of this panel and single gene analysis for any gene present on this panel are available. To modify this panel via CGPH, use the Inborn Errors of Immunity/Bone Marrow Failure/Telomeropathy/Pulmonary Fibrosis/Very Early Onset IBD/Pancreatitis disease state for step 1 on the Custom Gene Ordering Tool
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.
Additional Testing Requirements
For cord blood specimens: Maternal cell contamination (MCC) studies are available. Order MATCC / Maternal Cell Contamination, Molecular Analysis, Varies on both the cord blood and maternal specimens under separate order numbers. Cord blood testing will proceed without MCC studies, but results may be compromised if MCC is present.
Specimen Required
Patient Preparation: A previous hematopoietic stem cell transplant from an allogenic donor will interfere with testing. For information about testing patients who have received a hematopoietic stem cell transplant, call 800-533-1710.
Submit only 1 of the following specimens:
Specimen Type: Whole blood
Container/Tube:
Preferred: Lavender top (EDTA) or yellow top (ACD)
Acceptable: Green top (sodium heparin)
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 4 days/Frozen 4 days
Additional Information:
1. Specimens are preferred to be received within 4 days of collection. Extraction will be attempted for specimens received after 4 days, and DNA yield will be evaluated to determine if testing may proceed.
2. To ensure minimum volume and concentration of DNA is met, the requested volume must be submitted. Testing may be canceled if DNA requirements are inadequate.
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: Ambient (preferred) <24 hours/Refrigerated <24 hours
Additional Information:
1. Specimens are preferred to be received within 24 hours of collection. Culture and extraction will be attempted for specimens received after 24 hours and will be evaluated to determine if testing may proceed.
2. A separate culture charge will be assessed under CULFB / Fibroblast Culture for Biochemical or Molecular Testing. An additional 3 to 4 weeks are required to culture fibroblasts before genetic testing can occur.
Specimen Type: Cultured fibroblasts
Source: Skin
Container/Tube: T-25 flask
Specimen Volume: 2 Flasks
Collection Instructions: Submit confluent cultured fibroblast cells from a skin biopsy. Cultured cells from a prenatal specimen will not be accepted.
Specimen Stability Information: Ambient (preferred) <24 hours/Refrigerated <24 hours
Additional Information:
1. Specimens are preferred to be received within 24 hours of collection. Culture and extraction will be attempted for specimens received after 24 hours and will be evaluated to determine if testing may proceed.
2. A separate culture charge will be assessed under CULFB / Fibroblast Culture for Biochemical or Molecular Testing. An additional 3 to 4 weeks are required to culture fibroblasts before genetic testing can occur.
Specimen Type: Extracted DNA
Container/Tube:
Preferred: Screw Cap Micro Tube, 2 mL with skirted conical base
Acceptable: Matrix tube, 1 mL
Collection Instructions:
1. The preferred volume is at least 100 mcL at a concentration of 75 ng/mcL.
2. Include concentration and volume on tube.
Specimen Stability Information: Frozen (preferred) 1 year/Ambient/Refrigerated
Additional Information: DNA must be extracted in a CLIA-certified laboratory or equivalent and must be extracted from a specimen type listed as acceptable for this test (including applicable anticoagulants). Our laboratory has experience with Chemagic, Puregene, Autopure, MagnaPure, and EZ1 extraction platforms and cannot guarantee that all extraction methods are compatible with this test. If testing fails, one repeat will be attempted, and if unsuccessful, the test will be reported as failed and a charge will be applied. If applicable, specific gene regions that were unable to be interrogated due to DNA quality will be noted in the report.
Specimen Type: Bone marrow aspirate
Container/Tube:
Preferred: Lavender top (EDTA)
Acceptable: Yellow top (ACD)
Specimen Volume: 2 mL
Collection Instructions:
1. Invert several times to mix bone marrow.
2. Send bone marrow specimen in original tube. Do not aliquot.
3. Label specimen as bone marrow.
Specimen Stability Information: Ambient (preferred) 4 days/Refrigerate 4 days/Frozen 4 days
Additional Information:
1. Specimens are preferred to be received within 4 days of collection. Extraction will be attempted for specimens received after 4 days, and DNA yield will be evaluated to determine if testing may proceed.
2. To ensure minimum volume and concentration of DNA is met, the requested volume must be submitted. Testing may be canceled if DNA requirements are inadequate.
Specimen Type: Cord blood
Container/Tube:
Preferred: Lavender top (EDTA) or yellow top (ACD)
Acceptable: Green top (sodium heparin)
Specimen Volume: 3 mL
Collection Instructions:
1. Invert several times to mix blood.
2. Send cord blood specimen in original tube. Do not aliquot.
Specimen Stability Information: Ambient (preferred) 4 days/Refrigerated 4 days/Frozen 4 days
Additional Information:
1. Specimens are preferred to be received within 4 days of collection. Extraction will be attempted for specimens received after 4 days, and DNA yield will be evaluated to determine if testing may proceed.
2. To ensure minimum volume and concentration of DNA is met, the requested volume must be submitted. Testing may be canceled if DNA requirements are inadequate.
3. While a properly collected cord blood sample may not be at risk for maternal cell contamination, unanticipated complications may occur during collection. Therefore, maternal cell contamination studies are recommended to ensure the test results reflect that of the patient tested and are available at an additional charge. Order MATCC / Maternal Cell Contamination, Molecular Analysis, Varies on the maternal specimen.
Specimen Type: Blood spot
Supplies: Card-Blood Spot Collection (Filter Paper) (T493)
Container/Tube:
Preferred: Collection card (Whatman Protein Saver 903 Paper)
Acceptable: PerkinElmer 226 filter paper or blood spot collection card
Specimen Volume: 2 to 5 Blood spots
Collection Instructions:
1. An alternative blood collection option for a patient older than 1 year is a fingerstick. For detailed instructions, see How to Collect a Dried Blood Spot Sample.
2. Let blood dry on the filter paper at ambient temperature in a horizontal position for a minimum of 3 hours.
3. Do not expose specimen to heat or direct sunlight.
4. Do not stack wet specimens.
5. Keep specimen dry
Specimen Stability Information: Ambient (preferred)/Refrigerated
Additional Information:
1. Blood spot specimens are acceptable but not recommended. Multiple extractions will be required to obtain sufficient yield for supplemental analysis, and there is significant risk for test failure due to insufficient DNA.
2. Due to lower concentration of DNA yielded from blood spot, some aspects of the test may not perform as well as DNA extracted from a whole blood sample. When applicable, specific gene regions that were unable to be interrogated will be noted in the report. Alternatively, additional specimen may be required to complete testing.
3. For collection instructions, see Blood Spot Collection Instructions
4. For collection instructions in Spanish, see Blood Spot Collection Card-Spanish Instructions (T777)
5. For collection instructions in Chinese, see Blood Spot Collection Card-Chinese Instructions (T800)
Specimen Type: Saliva
Patient Preparation: Patient should not eat, drink, smoke, or chew gum 30 minutes prior to collection.
Supplies: Saliva Swab Collection Kit (T786)
Specimen Volume: 2 Swabs, use 2 kits for collection
Collection Instructions: Collect and send specimen per kit instructions.
Specimen Stability Information: Ambient (preferred) 30 days/Refrigerated 30 days
Additional Information: Saliva specimens are acceptable but not recommended. Due to lower quantity/quality of DNA yielded from saliva, some aspects of the test may not perform as well as DNA extracted from a whole blood sample. When applicable, specific gene regions that were unable to be interrogated will be noted in the report. Alternatively, additional specimen may be required to complete testing.
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)
Secondary ID
621561Useful For
Providing a comprehensive genetic evaluation for patients with a personal or family history suggestive of a hereditary bone marrow failure syndrome
Establishing a diagnosis of a hereditary bone marrow failure syndrome associated with known causal genes
Identifying variants within genes known to be associated with heritable bone marrow syndromes, allowing for predictive testing of at-risk family members and/or determination of targeted management (anticipatory guidance, management changes, specific therapies)
Reflex Tests
Test ID | Reporting Name | Available Separately | Always Performed |
---|---|---|---|
CULFB | Fibroblast Culture for Genetic Test | Yes | No |
MATCC | Maternal Cell Contamination, B | Yes | No |
Testing Algorithm
Skin biopsy:
For skin biopsy or cultured fibroblast specimens, a fibroblast culture will be performed at an additional charge. If viable cells are not obtained, the client will be notified.
Cord blood:
For cord blood specimens that have an accompanying maternal blood specimen, maternal cell contamination studies will be performed at an additional charge.
Special Instructions
- Informed Consent for Genetic Testing
- Blood Spot Collection Card-Spanish Instructions
- Blood Spot Collection Card-Chinese Instructions
- Informed Consent for Genetic Testing (Spanish)
- Blood Spot Collection Instructions
- Congenital Neutropenia, Bone Marrow Failure, Telomere Defects, and Pulmonary Fibrosis (IPF) Patient Information
- Targeted Genes and Methodology Details for Inherited Bone Marrow Failure Gene Panel
Method Name
Sequence Capture and Amplicon-Based Next-Generation Sequencing (NGS) followed by Droplet Digital Polymerase Chain Reaction (ddPCR)/Quantitative Real-Time Polymerase Chain Reaction (qPCR) and Sanger Sequencing as needed
Reporting Name
Bone Marrow Failure Gene PanelSpecimen Type
VariesSpecimen Minimum Volume
See Specimen Required
Specimen Stability Information
Specimen Type | Temperature | Time |
---|---|---|
Varies | Varies |
Reject Due To
All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.Clinical Information
Bone marrow failure (BMF) is characterized by the inadequate production of peripheral blood cells, resulting in single cytopenias or pancytopenia. BMF is associated with a loss, or deficient function, of hematopoietic stem or progenitor cells that may occur from a variety of acquired causes including aplastic anemia, myelodysplasia, environmental factors, drugs, and infections. BMF may also be caused by inherited or de novo genetic variants in one or more genes involved in hematopoiesis or bone marrow function.
The genetic landscape of inherited BMF is broad. For instance, some of the commonly recognized forms of inherited BMF include Fanconi anemia (caused by germline variants in one of several genes, such as FANCA and FANCC), Schwachman-Diamond syndrome (caused by variants in SBDS, DNAJC21, EFL1, SRP54), dyskeratosis congenita (caused by variants in one of multiple genes related to telomere biology, such as DKC1 and TINF2), and Diamond-Blackfan anemia (caused by variants in one of multiple genes encoding ribosomal subunits, such as RPS19). Other BMF disorders also include GATA2 deficiency (GATA2), MIRAGE (myelodysplasia, infection, growth restriction, adrenal hypoplasia, genital phenotypes, and enteropathy) syndrome (SAMD9), ataxia-pancytopenia syndrome (SAMD9L), severe congenital neutropenia (ELANE, HAX1, G6PC3, GFI1, and others) and congenital amegakaryocytic thrombocytopenia (MPL). In addition to these classically recognized BMF syndromes, variants in a broad spectrum of other genes are associated with inherited forms of cytopenias and BMF.
A suspicion for BMF should be raised by the identification of cytopenias with or without related clinical features such as infections, bleeding diathesis, fatigue, pallor, or dyspnea. In addition to hematologic findings, certain inherited BMF syndromes present with additional phenotypic and syndromic features. Importantly, several inherited BMF disorders also confer a predisposition to myeloid malignancies, such as myelodysplastic syndrome and acute myeloid leukemia, as well as other malignancies.
The diagnostic investigation of suspected BMF should include a bone marrow study. Bone marrow findings may be variable yet may include abnormalities in cellularity and dysplastic features. In patients with severely reduced cellularity and apparent aplastic anemia, a genetic etiology should also be considered. The investigation of suspected inherited BMF may also include functional screens, such as assessment of chromosomal breakage and telomere length analysis. Other tests, including viral studies and evaluation for autoimmune conditions or toxins, may also be performed to identify alternate causal factors. Nonetheless, the differential diagnosis of unilineage and multilineage cytopenias is broad, and distinguishing inherited forms of BMF from other underlying etiologies may be challenging. Next-generation sequencing-based genetic panels may be useful in the diagnostic investigation of suspected BMF in concert with the testing and screens described above.
Genetic testing for a possible inherited BMF syndrome may be considered in the setting of unexplained peripheral blood cytopenias and bone marrow abnormalities, especially when present during infancy or childhood, although contributory germline variants may be present in adults with BMF as well. The presence of extra hematopoietic features associated with syndromic forms of inherited BMF, such as skeletal abnormalities, leukoplakia, or pancreatic exocrine insufficiency, may also warrant testing. Furthermore, a myeloid malignancy arising at a young age also suggests an underlying genetic etiology, and there is increasing recognition that germline variants in genes associated with inherited forms of BMF also result in predisposition to hematological malignancies in adults. Alternatively, a family history of the clinical features or conditions described above may also suggest an underlying genetic basis for BMF.
In addition to diagnostic considerations, the identification of underlying hereditary variants in BMF carries important management implications. For instance, it may inform surveillance for malignancies and organ dysfunction in the setting of variants in genes associated with a risk for other clinical features and complications. Additionally, several forms of inherited BMF may confer a predisposition to myeloid malignancies that exhibit distinct sensitivity to cytotoxic therapy. Accordingly, the detection of certain germline variants may also guide treatment approaches including the selection of systemic therapy and conditioning regimens for hematopoietic stem cell transplantation. The identification of underlying inherited variants is also important for the optimal choice of donors for transplantation as related donors may share deleterious variants. Finally, detection of germline genetic variants associated with disease allows for familial testing to identify other individuals at risk of developing disease.
Note that testing of peripheral blood in patients with bone marrow failure, particularly in the setting of hematopoietic malignancy, may identify germline genetic variants and/or somatic mutations. This test is unable to definitively differentiate between germline variants and somatic mutations when performed on blood, bone marrow, or saliva specimens; however, testing may be performed on fibroblasts derived from a skin biopsy to aid in this differentiation.
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.
CPT Code Information
81441
LOINC Code Information
Test ID | Test Order Name | Order LOINC Value |
---|---|---|
BMFGP | Bone Marrow Failure Gene Panel | In Process |
Result ID | Test Result Name | Result LOINC Value |
---|---|---|
621562 | Test Description | 62364-5 |
621563 | Specimen | 31208-2 |
621564 | Source | 31208-2 |
621565 | Result Summary | 50397-9 |
621566 | Result | 82939-0 |
621567 | Interpretation | 69047-9 |
621568 | Additional Results | 82939-0 |
621569 | Resources | 99622-3 |
621570 | Additional Information | 48767-8 |
621571 | Method | 85069-3 |
621572 | Genes Analyzed | 82939-0 |
621573 | Disclaimer | 62364-5 |
621574 | Released By | 18771-6 |
MG153 | Is this Bone Marrow | 31208-2 |