Fanconi anemia is a rare autosomal recessive disorder characterized clinically 
by congenital abnormalities, progressive bone marrow failure, and a 
predisposition to malignancy. FA cells are sensitive to DNA cross-linking 
agents. Complementation analysis of FA cells using somatic cell fusion has 
facilitated the identification of eight complementation groups, suggesting that 
FA is a genetically heterogeneous disorder. Six genes (FANCA, FANCC, FANCD2, 
FANCE, FANGF, FANCG) have been cloned so far. The majority of affected patients 
belong to FA group A. Of the 32 unrelated Israeli patients with FA that we 
studied, 6 carried the FANCC mutations and 15 the FANCA mutations. Among the 
Jewish patients, ethnic-related mutations were common. Recent cumulative 
evidence suggests that the FA proteins are repair proteins. FANCC, FANCA and 
FANCG bind and interact in a protein complex found in the cytoplasm and nucleus 
of normal cells. FANCD2 exists in two isoforms; the long active form, FANCD2-L, 
is absent from FA cells of all complementation groups. FANCD2 colocalizes with 
BRCA1 in nuclear foci, probably as part of a large genomic surveillance complex. 
Studies using FANCA and FANCC knockout mice suggest that bone marrow precursors 
express interferon-gamma hypersensitivity and show progressive apoptosis. The 
definition of the molecular basis of FA in many affected families now enables 
prenatal diagnosis.