title: Blood oxidative stress and metallothionein expression in Rett syndrome: Probing for markers.
abstract: 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 MECP2 gene mutations with respect to healthy controls, and to explore novel blood antioxidant markers for RTT severity.
  
  
  
  In erythrocytes from RTT females aged 2-14 years (n = 27) and age-matched controls (n = 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.
  
  
  
  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.
  
  
  
  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 MECP2 mutation and specific clinical features led us to draw some interesting conclusions.
authors.affiliation: a DINOGMI, Dipartimento Di Neuroscienze , Riabilitazione, Oftalmologia, Genetica E Scienze Materno-Infantili, Università Di Genova , Genova , Italy .|b Unità Di Neuropsichiatria Infantile, Istituto Giannina Gaslini , Genova , Italy .
authors.forename: Maria
authors.initials: M
authors.lastname: Pintaudi
authors.affiliation: a DINOGMI, Dipartimento Di Neuroscienze , Riabilitazione, Oftalmologia, Genetica E Scienze Materno-Infantili, Università Di Genova , Genova , Italy .|b Unità Di Neuropsichiatria Infantile, Istituto Giannina Gaslini , Genova , Italy .
authors.forename: Edvige
authors.initials: E
authors.lastname: Veneselli
authors.affiliation: c DISTAV, Dipartimento Di Scienze Della Terra , Dell'ambiente E Della Vita, Università Di Genova , Genova , Italy .
authors.forename: Adriana
authors.initials: A
authors.lastname: Voci
authors.affiliation: d Centro Epilessia, Azienda Ospedaliera San Paolo, Dipartimento Di Scienze Della Salute , Università Degli Studi Di Milano , Milano , Italy .
authors.forename: Aglaia
authors.initials: A
authors.lastname: Vignoli
authors.affiliation: e Clinica Pediatrica, Università Di Catania , Catania , Italy .
authors.forename: Dora
authors.initials: D
authors.lastname: Castiglione
authors.affiliation: b Unità Di Neuropsichiatria Infantile, Istituto Giannina Gaslini , Genova , Italy .|f Unità Di Epidemiologia E Biostatistica, Istituto Giannina Gaslini , Genova , Italy , and.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Calevo
authors.affiliation: c DISTAV, Dipartimento Di Scienze Della Terra , Dell'ambiente E Della Vita, Università Di Genova , Genova , Italy .
authors.forename: Elena
authors.initials: E
authors.lastname: Grasselli
authors.affiliation: c DISTAV, Dipartimento Di Scienze Della Terra , Dell'ambiente E Della Vita, Università Di Genova , Genova , Italy .
authors.forename: Milena
authors.initials: M
authors.lastname: Ragazzoni
authors.affiliation: g Laboratorio Di Citogenetica E Genetica Molecolare, I.R.C.C.S. Istituto Auxologico Italiano , Milano.
authors.forename: Francesca
authors.initials: F
authors.lastname: Cogliati
authors.affiliation: g Laboratorio Di Citogenetica E Genetica Molecolare, I.R.C.C.S. Istituto Auxologico Italiano , Milano.
authors.forename: Luciano
authors.initials: L
authors.lastname: Calzari
authors.affiliation: d Centro Epilessia, Azienda Ospedaliera San Paolo, Dipartimento Di Scienze Della Salute , Università Degli Studi Di Milano , Milano , Italy .
authors.forename: Giulia Federica
authors.initials: GF
authors.lastname: Scornavacca
authors.affiliation: g Laboratorio Di Citogenetica E Genetica Molecolare, I.R.C.C.S. Istituto Auxologico Italiano , Milano.
authors.forename: Silvia
authors.initials: S
authors.lastname: Russo
authors.affiliation: c DISTAV, Dipartimento Di Scienze Della Terra , Dell'ambiente E Della Vita, Università Di Genova , Genova , Italy .
authors.forename: Laura
authors.initials: L
authors.lastname: Vergani
mesh_terms: D000293:Adolescent; D015415:Biomarkers; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008668:Metallothionein / Q000235:genetics / Q000378:metabolism*; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics*; D009154:Mutation; D018384:Oxidative Stress; D012044:Regression Analysis; D015518:Rett Syndrome / Q000235:genetics*
chemical_list: D015415:Biomarkers; C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2; D008668:Metallothionein
keywords: MECP2 gene mutation; Rett syndrome; metallothionein; methylome analysis; oxidative stress