Blood oxidative stress and metallothionein expression in Rett syndrome: Probing for markers

<p><i>Objectives</i>: Oxidative stress seems to be involved in Rett syndrome (RTT). The aim of this study was to assess the antioxidant status in RTT children with <i>MECP2</i> gene mutations with respect to healthy controls, and to explore novel blood antioxidant markers for RTT severity. <i>Methods</i>: In erythrocytes from RTT females aged 2–14 years (<i>n</i> = 27) and age-matched controls (<i>n</i> = 27), we measured the levels of malonaldehyde and the activity of two antioxidant enzymes, Cu/Zn-superoxide dismutase and catalase, by spectrophotometric assays. In leukocytes, the expression of metallothioneins, the main non-enzymatic antioxidants, was assessed by real-time RT-PCR. In nine selected RTT children, methylome analysis was also performed. <i>Results</i>: Blood of RTT patients showed increased lipid peroxidation and a dysregulated pattern of MT expression, while enzymatic activities did not change significantly with respect to controls. Moreover, we observed no epigenetic dysregulation in CpG-enriched promoter regions of the analysed genes but significant hypomethylation in the random loci. <i>Conclusions</i>: As the haematic level of MT-1A directly correlates with the phenotype severity, this metallothionein can represent a marker for RTT severity. Moreover, the attempt to link the level of blood oxidative stress with <i>MECP2</i> mutation and specific clinical features led us to draw some interesting conclusions. </p>