Early diagnosis of ataxia-telangiectasia using radiosensitivity testing.
OBJECTIVE
To utilize radiosensitivity testing to improve early diagnosis of patients with ataxia-telangiectasia (A-T).


METHODS
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.
Sun
Xia
X
Department of Pathology, UCLA School of Medicine, Los Angeles, California 90095-1732, USA.
Becker-Catania
Sara G
SG
Chun
Helen H
HH
Hwang
Mee Jeong
MJ
Huo
Yong
Y
Wang
Zhijun
Z
Mitui
Midori
M
Sanal
Ozden
O
Chessa
Luciana
L
Crandall
Barbara
B
Gatti
Richard A
RA
D001260:Ataxia Telangiectasia / Q000175:diagnosis* / Q000235:genetics; D002470:Cell Survival; D002478:Cells, Cultured / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D009154:Mutation; D010766:Phosphorylation; D011836:Radiation Tolerance / Q000235:genetics*; D012016:Reference Values; D012680:Sensitivity and Specificity; D000509:alpha-Fetoproteins / Q000032:analysis
D000509:alpha-Fetoproteins