Early diagnosis of ataxia-telangiectasia using radiosensitivity testing.

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.