OBJECTIVES: To utilize radiosensitivity testing to improve early diagnosis of patients with ataxia-telangiectasia (A-T). STUDY DESIGN: We established normal ranges for the colony survival assay (CSA) by testing cells from 104 patients with typical A-T, 29 phenotypic normal patients, and 19 A-T heterozygotes. We also analyzed 61 samples from patients suspected of having A-T and 25 patients with related disorders to compare the CSA with other criteria in the diagnosis of A-T. RESULTS: When cells were irradiated with 1.0 Gy, the mean survival fraction (microSF +/- 1 SD) for patients with A-T was 13.1% +/- 7.2% compared with 50.1% +/- 13.5% for healthy control patients. These data served to define a diagnostic range for the CSA (ie, <21%), a normal range (>36%), and a nondiagnostic intermediate range of 21% to 36%. The mutations of patients with A-T with intermediate radiosensitivity tended to cluster around the functional domains of the ATM gene. CONCLUSIONS: The CSA is a useful adjunctive test for confirming an early clinical diagnosis of A-T. However, CSA is also abnormal in other chromosomal instability and immunodeficiency disorders.
OBJECTIVES: To utilize radiosensitivity testing to improve early diagnosis of patients with ataxia-telangiectasia (A-T). STUDY DESIGN: We established normal ranges for the colony survival assay (CSA) by testing cells from 104 patients with typical A-T, 29 phenotypic normal patients, and 19 A-T heterozygotes. We also analyzed 61 samples from patients suspected of having A-T and 25 patients with related disorders to compare the CSA with other criteria in the diagnosis of A-T. RESULTS: When cells were irradiated with 1.0 Gy, the mean survival fraction (microSF +/- 1 SD) for patients with A-T was 13.1% +/- 7.2% compared with 50.1% +/- 13.5% for healthy control patients. These data served to define a diagnostic range for the CSA (ie, <21%), a normal range (>36%), and a nondiagnostic intermediate range of 21% to 36%. The mutations of patients with A-T with intermediate radiosensitivity tended to cluster around the functional domains of the ATM gene. CONCLUSIONS: The CSA is a useful adjunctive test for confirming an early clinical diagnosis of A-T. However, CSA is also abnormal in other chromosomal instability and immunodeficiency disorders.
Authors: Mariko D DeWire; Chris Beltran; Frederick A Boop; Kathleen J Helton; David W Ellison; Peter J McKinnon; Amar Gajjar; Atmaram S Pai Panandiker Journal: J Clin Oncol Date: 2012-06-11 Impact factor: 44.544
Authors: Liutao Du; Refik Kayali; Carmen Bertoni; Francesca Fike; Hailiang Hu; Patrick L Iversen; Richard A Gatti Journal: Hum Mol Genet Date: 2011-05-16 Impact factor: 6.150
Authors: Andrea Prodosmo; Andrea De Amicis; Cecilia Nisticò; Mario Gabriele; Giuliana Di Rocco; Laura Monteonofrio; Maria Piane; Enrico Cundari; Luciana Chessa; Silvia Soddu Journal: J Clin Invest Date: 2013-02-01 Impact factor: 14.808
Authors: Jun Shen; Edward C Gilmore; Christine A Marshall; Mary Haddadin; John J Reynolds; Wafaa Eyaid; Adria Bodell; Brenda Barry; Danielle Gleason; Kathryn Allen; Vijay S Ganesh; Bernard S Chang; Arthur Grix; R Sean Hill; Meral Topcu; Keith W Caldecott; A James Barkovich; Christopher A Walsh Journal: Nat Genet Date: 2010-01-31 Impact factor: 38.330
Authors: Liutao Du; Robert Damoiseaux; Shareef Nahas; Kun Gao; Hailiang Hu; Julianne M Pollard; Jimena Goldstine; Michael E Jung; Susanne M Henning; Carmen Bertoni; Richard A Gatti Journal: J Exp Med Date: 2009-09-21 Impact factor: 14.307