Radiation-induced chromosomal aberrations in pediatric patients with inborn errors of immunity: a G₀-phase approach...

Understanding the radiosensitivity status of patients may provide crucial insight for planning personalized treatment when high doses of ionizing radiation are part of treatment regimen. This is particularly relevant in case of pediatric patients who are to undergo myeloablative conditioning prior to hematopoietic stem cell transplantation (HSCT). Assessment of cytogenetic aberrations following irradiation using conventional blood culture is standard approach for evaluating radiosensitivity. However, in certain disorders, cells often exhibit poor proliferation, leading to culture failure. In such instances, aberration assessment with G₀-phase premature chromosome condensation (G₀-PCC) without culture may provide a suitable alternative.

In the current study, we have assessed baseline and radiation induced chromosome aberrations among three pediatric candidates for HSCT who were diagnosed with rare inborn errors of immunity disorders; Fanconi anemia (FA), leukocyte adhesion deficiency-I (LAD I) and Wiskott-Aldrich syndrome (WAS) using the G₀-PCC with fluorescence in situ hybridization (G₀-PCC-FISH) assay.

Blood samples were exposed to 2 Gy gamma radiation. Baseline and radiation-induced chromosomal aberrations were quantified with G₀-PCC-FISH and compared with baselines from healthy controls.

All three cases demonstrated elevated radiation-induced aberration frequencies, indicating increased radiosensitivity and impaired DNA repair capacity.

These findings highlight the potential utility of G₀-PCC-FISH as a rapid tool for radiosensitivity assessment. Especially useful when metaphases are difficult obtain due to failing cultures.