Mosaic forms of ataxia telangiectasia

Ataxia telangiectasia (AT) is a severe hereditary autosomal recessive neurodegenerative disease associated with accelerated aging and caused by mutation in both alleles of the atm gene. This gene encodes a key protein of cell response to DNA damage—the ATM protein kinase. Normally, upon formation of DNA double strand breaks, ATM is autophosphorylated and its active form phospho-ATM (P-ATM) appears. Here, we describe a mosaic form of AT in which cells of the same patient with a normal atm gene exhibited the accumulation of P-ATM in response to DNA double-strand breaks-inducing factors whereas, in cells bearing a mutant form of atm , P-ATM was not detected. Epigenetic markers, such as the histone deacetylases SIRT1 and SIRT6, and trimethylated forms of histone H3, H3K9me3 and H3K27me3, were studied in the nuclei of primary fibroblasts derived from patients with different forms of AT, and an increase in the SIRT6 level was revealed.