Roberts syndrome (RS) is a rare
genetic disorder, characterized clinically by severe pre- and post-natal growth retardation and symmetric limb reduction
deformities. Some patients with RS have a distinctive abnormality of the constitutive
heterochromatin (the RS effect) which has been described as a premature separation of the paracentromeric and nucleolar organizing regions of the chromosomes and the distal portion of the long arm of the Y chromosome (German, 1979). These patients [denoted RS(+)] are clinically indistinguishable from the RS(-) patients who lack the cytogenetic marker for
Roberts syndrome. Recently, a mutant in Drosophila has been described which has both
heterochromatin undercondensation and
hypersensitivity to
mutagen treatment (Gatti et al., 1983). The authors suggested that the uncondensed
heterochromatin may be more accessible to damage by
mutagens. Thus, the present study was an investigation of the
mutagen sensitivity in
Roberts syndrome, to determine whether there is a similar relationship between abnormal
heterochromatin structure and
mutagen sensitivity. Plating efficiency experiments were performed with RS(+) fibroblasts, RS(-) fibroblasts, RS heterozygous fibroblasts and a large assortment of appropriate control cells. The RS fibroblasts with the
heterochromatin abnormality were consistently more sensitive (based on D10 values) to
mitomycin C treatment than were any of the other cell strains tested, including RS(-) cells. These results support the hypothesis that
mitomycin C sensitivity and abnormal
heterochromatin structure in
Roberts syndrome are related.