title: G2 chromosomal radiosensitivity in families with ataxia-telangiectasia.
abstract: 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.
authors.affiliation: Department of Human Genetics, Sackler School of Medicine, Tel-Aviv University, Israel.
authors.forename: Y
authors.initials: Y
authors.lastname: Shiloh
authors.forename: R
authors.initials: R
authors.lastname: Parshad
authors.forename: M
authors.initials: M
authors.lastname: Frydman
authors.forename: K K
authors.initials: KK
authors.lastname: Sanford
authors.forename: S
authors.initials: S
authors.lastname: Portnoi
authors.forename: Y
authors.initials: Y
authors.lastname: Ziv
authors.forename: G M
authors.initials: GM
authors.lastname: Jones
mesh_terms: D001260:Ataxia Telangiectasia / Q000235:genetics*; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000528:radiation effects; D006580:Genetic Carrier Screening; D006801:Humans; D007399:Interphase / Q000528:radiation effects*; D008297:Male; D010375:Pedigree; D012016:Reference Values; D012867:Skin / Q000473:pathology / Q000528:radiation effects; D014965:X-Rays