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: 
 www.cincinnatichildrens.org/FanconiTesting

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

Methodology:

A customized CytoSure “exon-centric” array (Oxford Gene Technology) will be used to detect deletions and duplications.  The targeted array has enhanced probes targeted to the exonic regions of FANCA.  The arrays are run using Agilent SureScan technology.

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

Saliva: 2 ORAgene Saliva Kits (OGR-500) used according to manufacturer instructions.  Please contact KDL Client Services for a Saliva Collection Kit for patients that cannot provide a blood sample.

Assisted Saliva: 4 ORAgene Assisted Saliva Kits (OGR-575) used according to manufacturer instructions.  Please contact KDL Client Services for an Assisted Saliva Collection Kit for patients that cannot provide a blood sample.

Skin Fibroblast: Punch Biopsy (cell cultures will be prepared at KDL and used for testing), or 2 T-25 confluent flasks

Prenatal:

  • Direct Amniotic Fluid (10-20mL)
  • Direct CVS
  • Cultured Amniocytes (2 T-25 flasks)
  • Cultured CVS (2 T-25 flasks)
  • Cultured Fetal Tissue: Product of Conception (2 T-25 flasks)
  • Cord Blood (1-2mL)

DNA: 5-10µg at a minimum of 60-100ng/µL (DNA must be extracted in a CLIA-certified laboratory or a laboratory meeting equivalent requirements as determined by the CAP and/or CMS)

Notice Regarding Molecular Genetic Testing on CVS or Amniotic Fluid Specimens:

  • Maternal cell rule-out testing will be performed on all prenatal specimens received.Please provide maternal blood in addition to the fetal specimen.Additional charges apply for the maternal cell rule-out test.
  • All genetic testing performed on Direct CVS or Direct Amniotic Fluid specimens will be confirmed on cell cultures prepared by Knight Diagnostic Laboratories.Cell cultures will be prepared from the specimen received.Additional charges apply for confirmatory testing.

For routine testing of blood and saliva (or DNA extracted from them), KDL does NOT accept samples from patients within two (2) weeks of a packed cell/platelet transfusion or within four (4) weeks of a whole blood transfusion.  For extraordinary circumstances, where testing must be performed outside of the above windows, please contact our lab.

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:

  • Keep specimen cool during transit, but do not ship on dry ice. 
  • Please use the cold pack provided in the KDL shipping kit. 
  • Ship the specimen overnight express, using the FedEx priority overnight label provided. 
  • Contact Client Services at (855) 535-1522 for shipping kits and instructions.

References:

Additional Info:

Related tests also performed in our laboratory:  Full Sanger sequencing of FANCA gene.

Prior to any genetic testing we recommend genetic counseling.  To receive forms and information about prenatal diagnostic testing, please contact Client Services at (855) 535-1522.

 

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