• Test Code:
    1450
  • Department:
  • Test Synonyms:
    FANCA Comprehensive AnalysisFA Complementation Group AFanconi AnemiaFanconi Group AFanconi SequencingFANCA
  • CPT Code(s):
    81479x2
Background:

Fanconi Anemia (FA) is characterized by bone marrow failure, increased risk for cancer, and physical abnormalities.  Progressive bone marrow failure is responsible for the most significant morbidity and mortality.  Clinically heterogeneous, FA individuals are at increased risk for acute myelogenous leukemia, myelodysplasia, and solid tumors of the neck, head, oral cavities, and gynecological system.  Congenital abnormalities are present in approximately 70% of FA patients and include: café au lait spots or hypopigmentation; short stature; radial ray defects; eye defects such as microphthalmia; malformations of the kidney, genitalia, heart, gastrointestinal tract, ears, and feet.  Currently, 15 genes have been identified that, when mutated, can cause FA.  The Fanconi complementation group A gene, or FANCA, is inherited in an autosomal recessive manner.  Mutations (small nucleotide variants as well as gross deletions/duplications) in FANCA are responsible for approximately 66% of all FA cases.

Reasons for Referral
:

  • Confirmation of clinical diagnosis in patients with classical or atypical FANCA.
  • Carrier testing of family members of FANCA patients with known mutations.
  • Prenatal diagnosis.

Note: Prior to submitting a sample for FANCA molecular testing, cytogenetic confirmation of Fanconi anemia, by breakage analysis, is recommended and can be performed in the Knight Diagnostic Laboratories.

For breakage analysis please contact Client Services at (855) 535-1522 to obtain the correct requisition form to accompany the specimen.

Additionally, prior to molecular testing, complementation typing (complementation group assignment) is strongly recommended.  Complementation typing is available at a CLIA certified laboratory at the following URL address:
http://www.cincinnatichildrens.org/service/d/diagnostic-labs/cytogenetics/fanconi-anemia/.

Please attach the complementation group assignment documentation to the molecular testing requisition form, if possible.

Methodology:

Sequencing:    Sequencing for FANCA is carried out by amplification of all exons and intron/exon boundaries followed by bi-directional Sanger sequencing.  The sensitivity of full gene sequencing is estimated to be approximately 99% for single nucleotide substitutions and small insertions/deletions.  All nucleotide changes are analyzed within the context of current databases and literature to predict pathogenicity.

Deletion/Duplication: Large deletions and duplications are detected using multiplex ligation-dependent probe amplification (MLPA).

Test reporting follows the ACMG Standards & Guidelines for Clinical Genetics Laboratories, Ultra-Rare Disorders Guidelines, and Interpretation of Sequence Variants Guidelines.

Specimen Requirements:

Blood: Lavender tube (EDTA) or yellow (ACD)

    • Adult: 6mL
    • Child: 6mL
    • Infant: 2mL

DNA: 10µg at a minimum of 100ng/µL

A REQUISITION FORM MUST ACCOMPANY ALL SAMPLES.  Please include detailed clinical information, including ethnicity, clinical history, and family history.

Test Performed (Days):

Weekly

Turn Around Time:

14 – 21 Days

Shipment Sensitivity Requirements:

Package and ship specimen to remain cold, but not frozen.  Ship via overnight express, using the FedEx priority overnight label provided.  Contact Client Services for shipping kits and instructions at (855) 535-1522.

References:

Additional Info:

The Knight Cancer Institute at Oregon Health & Science University is a pioneer in the field of precision cancer medicine. The institute's director, Brian Druker, M.D., helped prove it was possible to shut down just the cells that enable cancer to grow. This breakthrough has made once-fatal forms of the disease manageable and transformed how cancer is treated. The OHSU Knight Cancer Institute is the only National Cancer Institute-designated Cancer Center between Sacramento and Seattle – an honor earned only by the nation's top cancer centers. It is headquarters for one of the National Cancer Institute's largest research collaboratives, SWOG, in addition to offering the latest treatments and technologies as well as hundreds of research studies and clinical trials.

Learn More