Introduction

Fanconi's anemia (FA) was originally described as an autosomal recessive disorder, characterized by progressive pancytopenia, diverse congenital abnormalities, and increased predisposition to malignancy (Auerbach et al., 1989). FA cells show a high level of chromosomal breakage, both spontaneously and induced by crosslinking agents such as mitomycin C, nitrogen mustard, diepoxybutane or photoactivated psoralens (Auerbach and Wolman, 1976; Berger et al., 1980). At least eight genetic complementation groups (A–H) have been described (Joenje et al., 1995). Genes for groups A, C, D, and G have been localized to chromosomes 16q24.3, 9q22.3, 3p, and 9p13, respectively, but the complementary deoxyribonucleic acid (cDNA) has been cloned and sequenced only for groups C (FANC), A (FANCA) and G (FANG) (de Winter et al., 1998; Fanconi Anaemia/Breast Cancer Consortium, 1996; Lo Ten Foe et al., 1996; Strathdee et al., 1992a,b; Whitney et al., 1995).

FA is a heterogeneous disorder that varies in both the genotype and phenotype (Gillio et al., 1997). Bone marrow failure is the most frequent hematological abnormality, occurring typically around 5 years of age, but aplasia can occur in older patients. Clonal abnormalities, including a high frequency of monosomy 7 and duplications involving 11q, can be observed on marrow cytogenetic analysis, as a sign of transformation to myelodysplastic syndrome or acute myeloblastic leukemia (Auerbach and Allen, 1991; Butturini et al., 1994). Bone marrow studies, including clonogeneic assays and long-term marrow cultures, show that the hemopoietic stem-cell pool gets smaller without gross defects in its microenvironment (Stark et al., 1993a).