2018 Jan;438(1-2):153-166. doi: 10.1007/s11010-017-3122-x. Epub 2017 Jul 25.

Author information

Department of Biomolecular Sciences, University of Urbino "Carlo Bo", Via Saffi 2, 61029, Urbino, PU, Italy. michele.menotta@uniurb.it.
Department of Biomolecular Sciences, University of Urbino "Carlo Bo", Via Saffi 2, 61029, Urbino, PU, Italy.
Department of Clinical and Molecular Medicine, Sapienza Università di Roma, Rome, Italy.
Department of Pediatrics and Child Neurology and Psychiatry, Sapienza Università di Roma, Rome, Italy.
Department of Clinical and Experimental Sciences, Pediatrics Clinic and Institute of Molecular Medicine "A. Nocivelli", Spedali Civili and University of Brescia, Brescia, Italy.


Ataxia telangiectasia (AT) is a rare incurable genetic disease caused by biallelic mutations in the Ataxia telangiectasia-mutated gene. Intra-erythrocyte infusion of dexamethasone improves clinical outcomes in AT patients; however, the molecular mechanisms that lead to this improvement remain unknown. Hence, to gain a better understanding of these mechanisms, we assessed the effects of glucocorticoid administration on gene expression in the blood of AT patients. Whole blood was obtained from nine children enrolled in a phase two clinical trial, who were being treated with dexamethasone (AT Dexa), from six untreated AT patients (AT) and from six healthy volunteers (WT). CodeLink Whole Genome Bioarrays were used to assess transcript expression. The reliability of the differentially expressed genes (DEGs) was verified by qRT-PCR analysis. The enriched Gene Ontology (GO) terms and the pathways of the Kyoto Encyclopedia of Genes and Genomes (KEGG) of DEGs obtained by group comparisons were achieved using the Database for Annotation, Visualization and Integrated Discovery (DAVID). Functional network analyses were computed by Reactome FI. The likely involved transcription factors were revealed by iRegulon. Among the identified DEGs influenced by the pathology and restored by dexamethasone, we detected 522 upregulated probes coding for known proteins, while 22 probes were downregulated, as they were in healthy subjects. These results provide useful information and represent a first step towards gaining a better understanding of the underlying mechanisms of the effects of dexamethasone on AT patients.


A-T; Ataxia telangiectasia; Dexamethasone; Erythrocyte delivery; Functional networks; Microarray

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