Chromosome instability with bleomycin and X-ray hypersensitivity in a boy with Nijmegen breakage syndrome

We report on a Mexican boy with microcephaly, short stature, and a high frequency of chromosome aberrations with rearrangements involving chromosomes 7 and 14, typical of ataxia telangiectasia (AT) patients. He had neither ataxia nor telangiectasia, and his immunological status and serum alpha feto protein (AFP) level were normal. Bleomycin hypersensitivity, which has been demon-strated in AT patients, was tested in the patient using AT and normal subjects for comparison. The frequency of spontaneously occurring chromosome aberrations in lymphocyte cultures was significantly higher in the patient and the AT patient than in the normal subject. Four cells from the patient showed structural rearrangements involving chromosomes 7 or 14, with breakpoints typical for AT. When exposed to 5.0 micrograms bleomycin, the lymphocytes from the AT patient showed the highest sensitivity to this agent; our patient had an intermediate sensitivity. In both patients several rearrangements involving chromosomes 7 and 14 were scored, while none were observed in the normal subject. A colony survival assay (CSA) [Huo et al., 1994: Cancer Res 54:2544-2547], using a lymphoblastoid cell line (LCL) derived from our patient, showed a survival fraction (SF) of 7%, which is in the same range as in AT patients. The clinical picture, together with the cytogenetic and radiosensitivity results, suggests that our patient fits the variable spectrum of Nijmegen breakage syndrome.