Molecular and cellular biology of Fanconi anemia.

Fanconi anemia (FA) is an autosomal recessive disorder characterized by progressive pancytopaenia, a diverse assortment of congenital malformations, and a predisposition to the development of malignancies. The extensive clinical heterogeneity observed in FA is reflected in genetic heterogeneity; the existence of 4 complementation groups has been inferred from complementation analysis. FA is putatively characterized as a DNA repair disorder since cells derived from patients are hypersensitive to DNA cross-linking agents. Although the primary defects in FA are not known, biochemical evidence supports either a direct defect in the removal of DNA cross-links or a defect in the ability of cells to respond to oxidative stress resulting from the interaction with cross-linking agents. Confirmation of either hypothesis awaits the cloning of genes defective in FA; some of the strategies to this end are discussed.