[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 atm gene. This gene encodes a key protein of cell response to DNA damage--an 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 normal atm gene demonstrated 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. The epigenetic markers such as 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 the increase of SIRT6 level was revealed.