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Exclusion/confirmation of Ataxia-telangiectasia via cell-cycle testing

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Ataxia telangiectasia (AT) is an autosomal recessive multisystem disorder with increased radiosensitivity and cancer susceptibility. The responsible gene (ATM) consists of 66 exons and a coding region of 9171 bp which precludes direct sequencing as a screening assay for confirmation or exclusion of the clinical suspicion of AT. Peripheral blood mononuclear cells of 330 patients referred for the exclusion of AT were exposed to ionizing radiation (IR) and incubated for 72 h in the presence of phytohemagglutinin. Using bivariate BrdU-Hoechst/ethidium bromide flowcytometry, the following cell cycle parameters were ascertained: (1) proportion of non-proliferating (G0,G1) cells as a measure of mitogen response, (2) proportion of first-cycle G2-phase cells relative to the growth fraction (G2/GF) as a measure of radiosensitivity. Of the cases tested, 94.2% could be unequivocally assigned either to the AT-negative or the AT-positive group of patients. Of the AT-positive cases, 11 were confirmed by ATM mutation analysis. Nineteen cases presented with non-conclusive results, mostly due to poor mitogen response; however, a combination of cell-cycle data with serum AFP concentrations led to the exclusion of AT in all but two of the uncertain cases. Substitution of ionizing radiation by the radiomimetic bleomycin was additionally tested in a small series of patients. We conclude that cell-cycle testing complemented by serum AFP measurements fulfills the criteria as a rapid and economical screening procedure for the differential diagnosis of juvenile ataxias.

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ataxia telangiectasia mutated


G2 phase of cell cycle


G0, G1 phase of cell cycle


Growth fraction (proliferating cells minus G0,G1 cells)


Ionizing radiation


Nijmegen breakage syndrome


Peripheral blood lymphocytes




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The authors would like to thank Professor Michael Flentje, Department of Radiation Therapy, University of Wurzburg School of Medicine, for providing access to and help with the X‐irradiation of patient lymphocyte samples.

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Correspondence to Holger Hoehn.

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Heinrich, T., Prowald, C., Friedl, R. et al. Exclusion/confirmation of Ataxia-telangiectasia via cell-cycle testing. Eur J Pediatr 165, 250–257 (2006). https://doi.org/10.1007/s00431-005-0037-4

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  • Childhood ataxia
  • Ataxia telangiectasia
  • Cell cycle
  • Flowcytometry
  • Radiosensitivity
  • Alpha-fetoprotein