Test Code GATAS GATA-Binding Protein 2, GATA2, Full Gene Analysis, Next-Generation Sequencing, Varies
Ordering Guidance
For cases where the differential diagnosis remains broad, GATA2 may be evaluated as part of a gene panel. See HLHGP / Primary Hemophagocytic Lymphohistiocytosis (HLH) Gene Panel, Varies; SCCNP / Severe Congenital and Cyclic Neutropenia Gene Panel, Varies; or EBLPD / Epstein Barr Virus (EBV) Susceptibility and Lymphoproliferative Disorders Gene Panel, Varies.
Targeted testing for familial variants (also called site-specific or known variants testing) is available for variants identified in the GATA2 gene. See FMTT / Familial Variant, Targeted Testing, Varies. To obtain more information about testing option, call 800-533-1710.
Shipping Instructions
Specimen preferred to arrive within 96 hours of collection.
Specimen Required
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:
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) 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 fibroblasts
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. 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. GATA2 Gene Sequencing Patient Information (T811) is recommended.
Secondary ID
619802Useful For
Comprehensive evaluation of the GATA2 gene in patients with clinical or immunological symptoms suggestive of GATA-binding protein 2 (GATA2) deficiency
Screening family members of patients with confirmed GATA2 deficiency
Reflex Tests
Test ID | Reporting Name | Available Separately | Always Performed |
---|---|---|---|
CULFB | Fibroblast Culture for Genetic Test | Yes | No |
Testing Algorithm
For skin biopsy or cultured fibroblast specimens, fibroblast culture will be performed 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
Reporting Name
GATA2 Gene, Full Gene AnalysisSpecimen Type
VariesSpecimen Minimum Volume
Blood: 1 mL; Skin biopsy or cultured fibroblasts: See Specimen Required
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.Clinical Information
GATA-binding protein 2 (GATA2) deficiency causes multiple previously distinct clinical entities, including DCML deficiency (dendritic cell, monocyte, B and natural killer [NK] cell lymphocyte deficiency), MonoMAC syndrome (monocytopenia with Mycobacterium avium complex infection), Emberger syndrome (myelodysplastic syndrome [MDS] with lymphedema), NK cell deficiency, and familial MDS/acute myeloid leukemia. As such, there is a wide spectrum of clinical features, including severe viral infections (particularly with human papillomavirus, molluscum contagiosum, herpes simplex virus, Epstein-Barr virus, and cytomegalovirus), warts, fungal infections (particularly histoplasmosis and aspergillosis), mycobacterial infections, pulmonary alveolar proteinosis, bone marrow hypocellularity, neutropenia, sensorineural hearing loss, and congenital lymphedema. Immunological phenotypes include dendritic cell, monocyte, CD4+ T cell, B- and NK- cell deficiencies. Also, the loss of a specific NK-cell subset, CD56 bright NK cells, has been reported in these patients.
GATA2 is a zinc finger transcription factor involved in hematopoiesis, maintenance of the hematopoietic stem cell (HSC) pool, and for HSC progenitor differentiation. Disease-causing genetic variants in GATA2 result in loss-of-function and haploinsufficiency and are transmitted in an autosomal dominant manner or arise de novo. Null variants (frameshift, nonsense, splicing, and large deletions) account for most cases, while missense variants account for approximately 30% of cases, and noncoding variants in an intronic enhancer element and synonymous variants that impact splicing account for the remainder of cases. Genotype-phenotype correlations are difficult to make, as there is considerable clinical heterogeneity. Incomplete penetrance has been observed with GATA2 deficiency, and the age at presentation varies; however, by age 60 years, the penetrance is estimated to be 90%. Additionally, there may be a role for environmental factors triggering certain infectious manifestations.
The definitive treatment for GATA2 deficiency is HSC transplantation. Early genetic diagnosis of GATA2 deficiency may aid in selecting management strategies and allow for family screening and counseling.
Reference Values
An interpretive report will be provided
Interpretation
All detected variants are evaluated according to American College of Medical Genetics and Genomics (ACMG) 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 GATA2 gene, 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), and 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 GATA2 gene.
There may be regions of GATA2 gene 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)
Confirmation of select reportable variants may be performed by alternate methodologies based on internal laboratory criteria.
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.
Gene symbol |
Reference transcript |
Additional evaluations |
Technical limitations |
GATA2 |
NM_032638.5 |
c.1017+526_1017+589 corresponding to a highly conserved intronic region |
- |
Day(s) Performed
Varies
Performing Laboratory
Mayo Clinic Laboratories in RochesterTest Classification
This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.CPT Code Information
81479
88233- Tissue culture, skin, solid tissue biopsy (if appropriate)
88240- Cryopreservation (if appropriate)
LOINC Code Information
Test ID | Test Order Name | Order LOINC Value |
---|---|---|
GATAS | GATA2 Gene, Full Gene Analysis | 95771-2 |
Result ID | Test Result Name | Result LOINC Value |
---|---|---|
619803 | Test Description | 62364-5 |
619804 | Specimen | 31208-2 |
619805 | Source | 31208-2 |
619806 | Result Summary | 50397-9 |
619807 | Result | 82939-0 |
619808 | Interpretation | 69047-9 |
619809 | Additional Results | 82939-0 |
619810 | Resources | 99622-3 |
619811 | Additional Information | 48767-8 |
619812 | Method | 85069-3 |
619813 | Genes Analyzed | 82939-0 |
619814 | Disclaimer | 62364-5 |
619815 | Released By | 18771-6 |