2017 Jul 5;12(1):126. doi: 10.1186/s13023-017-0669-2.

Menotta M1Biagiotti S2Spapperi C2Orazi S2Rossi L2Chessa L3Leuzzi V4D'Agnano D4Soresina A5Micheli R5Magnani M2.

Author information

Department of Biomolecular Sciences, University of Urbino "Carlo Bo", 61029, Urbino, PU, Italy. michele.menotta@uniurb.it.
Department of Biomolecular Sciences, University of Urbino "Carlo Bo", 61029, Urbino, PU, Italy.
Department of Clinical and Molecular Medicine, University "La Sapienza", 00198, Rome, Italy.
Department of Pediatrics and Child Neurology and Psychiatry, University "La Sapienza", Rome, Italy.
Department of Clinical and Experimental Sciences, Pediatrics Clinic and Institute of Molecular Medicine "A. Nocivelli", Unit of Child Neurology and Psychiatry 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 (ATM) gene. Treatment with glucocorticoid analogues has been shown to improve the neurological symptoms that characterize this syndrome. Nevertheless, the molecular mechanism underlying the glucocorticoid action in AT patients is not yet understood. Recently, we have demonstrated that Dexamethasone treatment may partly restore ATM activity in AT lymphoblastoid cells by a new ATM transcript, namely ATMdexa1.


In the present study, the new ATMdexa1 transcript was also identified in vivo, specifically in the PMBCs of AT patients treated with intra-erythrocyte Dexamethasone (EryDex). In these patients it was also possible to isolate new "ATMdexa1 variants" originating from canonical and non-canonical splicing, each containing the coding sequence for the ATM kinase domain. The expression of the ATMdexa1 transcript family was directly related to treatment and higher expression levels of the transcript in patients' blood correlated with a positive response to Dexamethasone therapy. Neither untreated AT patients nor untreated healthy volunteers possessed detectable levels of the transcripts. ATMdexa1 transcript expression was found to be elevated 8 days after the drug infusion, while it decreased 21 days after treatment.


For the first time, the expression of ATM splicing variants, similar to those previously observed in vitro, has been found in the PBMCs of patients treated with EryDex. These findings show a correlation between the expression of ATMdexa1 transcripts and the clinical response to low dose dexamethasone administration.


ATM; ATMdexa1; Ataxia Telangiectasia; Dexamethasone; Intra-erythrocyte DEXA