Chromosome Analysis, DEB Assay for Fanconi Anemia

Test Code

14598

CPT Codes
88230, 88249

Physician Attestation of Informed Consent

This germline genetic test requires physician attestation that patient consent has been received if ordering medical facility is located in AK, DE, FL, GA, IA, MA, MN, NV, NJ, NY, OR, SD or VT or test is performed in MA.

Preferred Specimen

10 mL whole blood collected in a sodium heparin (green-top) tube
Infants: 3 mL whole blood collected in a pediatric (3 mL) vacutainer

Minimum Volume

2 mL

Other Acceptable Specimens

Whole blood collected in sodium heparin (royal blue-top or tan-top, lead free) tube

Instructions

Diagnostic test only. This test will not detect carriers of a Fanconi anemia gene mutation.

Clinical history and reason for referral are required with test order.

Specimen viability decreases during transit. Send specimen to testing lab for viability determination. Do not freeze. Do not reject.

This test may be canceled and replaced by: Chromosome Analysis, Blood, No Growth, if the specimen does not yield mitotically active cells for analysis; or with a Cytogenetics Communication, if a communication is required.

Transport Temperature

Room temperature

Specimen Stability

Room temperature: See Collection Instructions
Refrigerated: See Collection Instructions
Frozen: See Collection Instructions

Methodology
Chromosome Breakage (DEB) • Tissue Culture

Setup Schedule

Set up: Daily; Report available: 14 days

Limitations

This analysis only evaluates the amount of breakage in the cells and will not identify any specific mutation in the DNA. This test will reliably detect affected individuals but is not an appropriate test for unaffected carriers of the disorder. This test does not rule out numeric or structural chromosomal abnormalities. Some individuals with characteristics suggestive of FA may have normal results in the DEB chromosome breakage test, therefore, a negative DEB study does not rule out FA in all cases. This test will not rule out the possibility of birth defects such as those caused by chromosome abnormalities, mutations in other genes important in development, and environmental or in-utero exposures.

Reference Range

See Laboratory Report

Clinical Significance

This assay is a first-line screening test for patients with clinical suspicion of Fanconi anemia, an inherited disorder that causes chromosomal instability [1]. This test is not used to evaluate carrier status for Fanconi anemia or for prenatal testing.

Fanconi anemia is a multigenic and primarily autosomal recessive disorder caused by pathogenic variants that affect DNA repair. Populations with increased carrier frequencies for 1 or more of these pathogenic variants include individuals of Ashkenazi Jewish, Afrikaner, sub-Saharan African, Roma, or South Asian (Indian and Pakistan) descent [1]. Clinical manifestations of Fanconi anemia vary broadly and may include congenital abnormalities, bone marrow failure, predisposition to cancer, and severe toxicity to chemotherapy. Early diagnosis is critical for patient management, especially in severe cases [1].

This test evaluates chromosome breakage in cultured lymphocytes following treatment with diepoxybutane (DEB), a DNA cross-linking agent. Lymphocytes from patients with Fanconi anemia typically have an increased number of chromosomal breaks and aberrations. Clinical care guidelines for Fanconi anemia indicate that a positive test result should be followed by genetic testing to identify pathogenic variants; a negative test result with weak clinical suspicion may not require further testing; and an indeterminate (equivocal) result may be confirmed with a skin fibroblast chromosome breakage test [1].

Although chromosome breakage analysis performed with peripheral blood is considered the gold standard for laboratory diagnosis of Fanconi anemia [1], other rare chromosome breakage disorders can also cause positive results. These include Nijmegen breakage syndrome, Roberts syndrome, and Warsaw breakage syndrome.

The results of this test should be interpreted in the context of pertinent clinical and family history and physical examination findings.

Reference
1. Sroka I, et al, eds. Fanconi Anemia Clinical Care Guidelines. 5th ed. Fanconi Anemia Research Fund; 2020. Accessed April 19, 2022. https://www.fanconi.org/images/uploads/other/Fanconi_Anemia_Clinical_Care_Guidelines_5thEdition_web.pdf

Performing Laboratory

Quest Diagnostics Nichols Institute
14225 Newbrook Drive
Chantilly, VA 20153

The CPT Codes provided in this document are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payor being billed. Any Profile/panel component may be ordered separately. Reflex tests are performed at an additional charge.