{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T23:16:50Z","timestamp":1789514210938,"version":"build-2803163510"},"reference-count":38,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2008,4,22]],"date-time":"2008-04-22T00:00:00Z","timestamp":1208822400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cytometry Pt A"],"published-print":{"date-parts":[[2008,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Ataxia telangiectasia (A\u2010T) is a progressive neurodegenerative disease with onset in early childhood, caused by mutations in the <jats:italic>ATM<\/jats:italic> (ataxia\u2010telangiectasia mutated) gene. Diagnosis relies on laboratory tests showing high levels of serum alphafetoprotein, cell sensitivity to ionizing radiation (IR) and absence or reduced levels of ATM protein. Many tests, however, are not sufficiently sensitive or specific for A\u2010T, have long turnaround times, or require large blood samples. This prompted us to develop a new flow cytometry method for the diagnosis of A\u2010T based on the measurement of histone H2AX phosphorylation. We established normal ranges of histone H2AX phosphorylation after 2 Gy IR by testing T\u2010cell lines, lymphoblastoid cell lines (LCLs) and\/or peripheral blood mononuclear cells (PBMCs) or both from 20 genetically proven A\u2010T and 46 control donors. To further evaluate the specificity and sensitivity of the test, we analyzed cells from 19 patients suspected of having A\u2010T, and from one Friedreich Ataxia, one Ataxia with Oculomotor Apraxia type 2, and one Nijmegen Breakage Syndrome patients. Phosphorylated histone H2AX mean fluorescence intensity of irradiated A\u2010T cells was significantly lower than that of healthy donors. The intrastaining, intraassay, and interassay imprecisions were \u226413.22%. Sensitivity and specificity were virtually 100% when the test was performed on PBMCs. Screening of 19 consecutive new patients with suspected A\u2010T classified 15 patients as non\u2010A\u2010T and four as A\u2010T; diagnosis of the latter four was subsequently confirmed by DNA sequencing to identify <jats:italic>ATM<\/jats:italic> mutations. The Friedreich Ataxia patient, the Ataxia with Oculomotor Apraxia type 2 patient and the Nijmegen Breakage Syndrome patient were classified as non\u2010A\u2010T. This flow cytometry test is very sensitive, specific and rapid, and requires only 2 ml of blood. It may thus be proposed for the early differential diagnosis of A\u2010T as an alternative to methods requiring the production of LCLs. \u00a9 2008 International Society for Advancement of Cytometry<\/jats:p>","DOI":"10.1002\/cyto.a.20566","type":"journal-article","created":{"date-parts":[[2008,4,22]],"date-time":"2008-04-22T21:31:16Z","timestamp":1208899876000},"page":"508-516","source":"Crossref","is-referenced-by-count":52,"title":["A rapid flow cytometry test based on histone H2AX phosphorylation for the sensitive and specific diagnosis of ataxia 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