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.
Strathdee
C A
CA
Department of Genetics, Hospital for Sick Children, Toronto, Ontario, Canada.
Buchwald
M
M
D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D004260:DNA Repair; D005199:Fanconi Anemia / Q000145:classification / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005609:Free Radicals; D005808:Genes, Recessive; D005816:Genetic Complementation Test; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D015470:Leukemia, Myeloid, Acute / Q000235:genetics; D008297:Male; D010100:Oxygen / Q000378:metabolism; D011289:Preleukemia / Q000235:genetics; D015995:Prevalence; D014162:Transfection
D005609:Free Radicals; D004247:DNA; D010100:Oxygen