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 prec...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 seq uencing as a screening assay for confirmation or exclusion of the clinical suspi cion 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 i n the presence of phytohemagglutinin.Using bivariate BrdUHoechst/ethidium brom ide flowcytometry,the following cell cycle parameters were ascertained:(1)pro portion 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 unequ ivocally assigned either to the AT-negative or the AT-positive group of patien ts.Of the AT-positive cases,11 were confirmed by ATM mutation analysis.Ninet een cases presented with non-conclusive results,mostly due to poor mitogen res ponse;however,a combination of cellcycle data with serum AFP concentrations le d 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 sm all series of patients.We conclude that cell-cycle testing complemented by ser um AFP measurements fulfills the criteria as a rapid and economical screening pr ocedure for the differential diagnosis of juvenile ataxias.展开更多
文摘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 seq uencing as a screening assay for confirmation or exclusion of the clinical suspi cion 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 i n the presence of phytohemagglutinin.Using bivariate BrdUHoechst/ethidium brom ide flowcytometry,the following cell cycle parameters were ascertained:(1)pro portion 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 unequ ivocally assigned either to the AT-negative or the AT-positive group of patien ts.Of the AT-positive cases,11 were confirmed by ATM mutation analysis.Ninet een cases presented with non-conclusive results,mostly due to poor mitogen res ponse;however,a combination of cellcycle data with serum AFP concentrations le d 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 sm all series of patients.We conclude that cell-cycle testing complemented by ser um AFP measurements fulfills the criteria as a rapid and economical screening pr ocedure for the differential diagnosis of juvenile ataxias.
