The Comprehensive Center for Fanconi Anemia & The Cytogenetic Facility


There are 13 complementation group subtypes for Fanconi anemia. Each subtype involves a defect in a different gene. The genes for Fanconi type A, C, D2, E, F, and G have been identified. Mutations in many of these genes have been characterized. We are intensively investigating the role of each gene involved in Fanconi anemia. Dr. D'Andrea's research has identified a Fanconi biochemical pathway wherein the Fanconi A, C, E, F, and G proteins associate together in order to activate the Fanconi D2protein. The Fanconi D2protein associates with other proteins involved in DNA repair. We and others are studying the role of each Fanconi gene. The goal of elucidating the Fanconi biochemical pathway is the development of new effective therapies.

Our laboratory is performing subtyping analysis on a research basis. A small sample of blood (about one teaspoon) obtained at a time when blood is being drawn for clinical reasons can be used for these studies. The blood cells (lymphocytes) are immortalized with a virus (Epstein Barr virus or EBV, which is the virus that causes mononucleosis) and grown in culture for testing. The patient's subtype is identified by testing the ability of an introduced Fanconi gene (A, C, D2, E, F, or G) to correct the cell's sensitivity to DNA damaging agents such as mitomycin C (MMC) or diepoxybutane (DEB). Fanconi cells cannot repair the DNA damage inflicted by these agents. Introduction of the functional homologue of the defective Fanconi gene can restore the cell's ability to repair its DNA. The cells are then frozen and stored for additional studies. A family can choose to withdraw from these studies at any time.

These tests take several weeks to complete. Sometimes, cells from Fanconi patients do not grow well in culture. We would let you know if this were the case, and you would have the option of submitting another sample for testing.

We are currently developing a new rapid screen for subtyping analysis. We are working on tests that utilize our new knowledge of the Fanconi anemia biochemical pathway. Patient samples are critical for the advancement of this research.

It is important to be aware that these tests are research tests and have not been approved for clinical use. If these tests do become clinically available at some future time, the subtyping tests should be repeated in a clinically certified laboratory before they are used to guide clinical management.