The identification of fanconi anemia genotypes by clastogenic stress

Clastogen-induced chromosome damage was investigated in peripheral lymphocytes of five patients with Fanconi anemia (FA), 10 obligate heterozygotes, 25 normal controls, and four individuals with some clinical manifestations of FA. The two agents used were diepoxybutane (DEB) and mitomycin C (MMC), previously reported to be specific for the induction of increased chromosome breakage in FA cells. Following clastogenic stress, two of the five FA patients did not exhibit the expected increase in chromosomal damage while three of the four "non-FA" individuals did. In this series of subjects, the possibility of misdiagnosis is considerable when based on either clinical delineation or cytogenetic results alone. Therefore, the integration of both laboratory data and physical findings is essential before reaching a diagnosis. Furthermore, the broad range of response in both the control group and the parents of FA patients yields overlapping results, making reliable heterozygote detection impractical by these procedures.