Sultan Qaboos University Medical Journal (Mar 2019)

Individual Radiosensitivity Assessment of the Families of Ataxia-Telangiectasia Patients by G2-Checkpoint Abrogation

  • Asghar Aghamohammadi,
  • Seyed M. Akrami,
  • Marjan Yaghmaie,
  • Nima Rezaei,
  • Gholamreza Azizi,
  • Mehdi Yaseri,
  • Hassan Nosrati,
  • Majid Zaki-Dizaji

DOI
https://doi.org/10.18295/squmj.2018.18.04.003
Journal volume & issue
Vol. 18, no. 4
pp. 440 – 446

Abstract

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Objectives: Ataxia-telangiectasia (A-T) is an autosomal recessive multisystem disorder characterised by cerebellar degeneration, telangiectasia, radiation sensitivity, immunodeficiency, oxidative stress and cancer susceptibility. Epidemiological research has shown that carriers of the heterozygous ataxia-telangiectasia mutated (ATM) gene mutation are radiosensitive to ionising irradiation and have a higher risk of cancers, type 2 diabetes and atherosclerosis. However, there is currently no fast and reliable laboratory-based method to detect heterozygous ATM carriers for family screening and planning purposes. This study therefore aimed to evaluate the ability of a modified G2-assay to identify heterozygous ATM carriers in the families of A-T patients. Methods: This study took place at the Tehran University of Medical Sciences, Tehran, Iran, between February and December 2017 and included 16 A-T patients, their parents (obligate heterozygotes) and 30 healthy controls. All of the subjects underwent individual radiosensitivity (IRS) assessment using a modified caffeine-treated G2-assay with G2-checkpoint abrogation. Results: The mean IRS of the obligate ATM heterozygotes was significantly higher than the healthy controls (55.13% ± 5.84% versus 39.03% ± 6.95%; P <0.001), but significantly lower than the A-T patients (55.13% ± 5.84% versus 87.39% ± 8.29%; P = 0.001). A receiver operating characteristic (ROC) curve analysis of the G2-assay values indicated high sensitivity and specificity, with an area under the ROC curve of 0.97 (95% confidence interval: 0.95–1.00). Conclusion: The modified G2-assay demonstrated adequate precision and relatively high sensitivity and specificity in detecting heterozygous ATM carriers. Keywords: Ataxia-Telangiectasia; Chromosome Breakage; Genetic Carrier Screening; Heterozygote; Radiation Sensitivity; Sensitivity and Specificity.