Summary
An autosomal recessive disease associated with chromosomal instability, Fanconi's anemia (FA) is remarkable by its phenotypic heterogeneity, which includes bone-marrow failure, a variety of congenital malformations, a propensity to develop acute myeloid leukemia (AML) and cellular hypersensitivity to DNA cross-linking agents. This property has allowed the study of the mechanisms underlying the disease and also contributes to making the clinical diagnosis. FA has been found in all ethnic groups. Its frequency has been estimated to be 1/350,000 births. FA is characterized clinically by pancytopenia, progressive aplastic anemia, diverse congenital malformations and, above all, a marked predisposition to develop AML. The congenital anomalies include skeletal malformations, hyperpigmentation, urogenital, renal and cardiac anomalies. The hematological disorders resulting from bone marrow dysfunction (thrombocytopenia, progressive pancytopenia) usually appear around a mean age of 7 years, but they can arise very early, at birth, or, even more rarely, very late around 40 years of age. Bone-marrow or umbilical cord-blood transplantations are the main treatment, relatively effective, of the hematological failure typical of FA. Even if it is not yet effective, it seems that cellular therapy with isolated and characterized stem cells is a promising approach for FA patients. Analysis by in situ somatic hybridization, followed by the search for complementation for the cytotoxic response to DNA cross-linking agents, using lymphoblastoid cell lines, led to the identification of 8 complementation groups (FANCA-FANCH), each of which was thought to represent a unique gene. To date, 6 FANC genes have been cloned. A unified and precise understanding of the biochemical events responsible for FA is still lacking. The functions of the different FANC genes remain unknown. *Author: Dr E. Moustacchi (October 2003)*.
