Summary
Ataxia-telangiectasia (A-T) is an autosomal recessive disease involving chromosomal instability, susceptibility to cancer and X-ray hypersensitivity. The latter two features are expressed to a limited extent in the heterozygous carriers of A-T mutations. Although fibroblast lines from A-T heterozygotes clearly show increased susceptibility to the lethal effect of X-irradiation, the difference in post-irradiation survival between cell lines and normal controls is not always large enough to allow the use of X-ray sensitivity as a laboratory assay for carrier detection in A-T. Recently, we have shown in a blind study, that the extent of chromatid damage induced in the G2 phase of the cell cycle by moderate doses of X-rays is markedly higher in A-T heterozygous cells than in normal controls. We have now applied this test to 6 additional obligatory heterozygotes and 24 individuals with different risks of being A-T carriers, from three Israeli A-T families. All 6 cell lines from the obligatory heterozygotes showed the typical hypersensitivity to the clastogenic action of X-rays in G2; of the 24 cell lines with unknown A-T genotype, 16 showed the same hypersensitivity, and 8 responded in a normal way. The proportion of cell lines showing the “A-T-heterozygous phenotype” was in accord with the expected value, based on Mendelian chance calculations. Since these observations were made, a daughter of two hypersensitive parents in one of these families has been diagnosed as having A-T. This confirmed the presumed A-T heterozygosity of the parents, as indicated by the laboratory assay.
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Shiloh, Y., Parshad, R., Frydman, M. et al. G2 chromosomal radiosensitivity in families with ataxia-telangiectasia. Hum Genet 84, 15–18 (1989). https://doi.org/10.1007/BF00210663
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DOI: https://doi.org/10.1007/BF00210663