title: MECP2 Duplication Syndrome: Evidence of Enhanced Oxidative Stress. A Comparison with Rett Syndrome.
abstract: Rett syndrome (RTT) and MECP2 duplication syndrome (MDS) are neurodevelopmental disorders caused by alterations in the methyl-CpG binding protein 2 (MECP2) gene expression. A relationship between MECP2 loss-of-function mutations and oxidative stress has been previously documented in RTT patients and murine models. To date, no data on oxidative stress have been reported for the MECP2 gain-of-function mutations in patients with MDS. In the present work, the pro-oxidant status and oxidative fatty acid damage in MDS was investigated (subjects n = 6) and compared to RTT (subjects n = 24) and healthy condition (subjects n = 12). Patients with MECP2 gain-of-function mutations showed increased oxidative stress marker levels (plasma non-protein bound iron, intraerythrocyte non-protein bound iron, F2-isoprostanes, and F4-neuroprostanes), as compared to healthy controls (P ≤ 0.05). Such increases were similar to those observed in RTT patients except for higher plasma F2-isoprostanes levels (P < 0.0196). Moreover, plasma levels of F2-isoprostanes were significantly correlated (P = 0.0098) with the size of the amplified region. The present work shows unique data in patients affected by MDS. For the first time MECP2 gain-of-function mutations are indicated to be linked to an oxidative damage and related clinical symptoms overlapping with those of MECP2 loss-of-function mutations. A finely tuned balance of MECP2 expression appears to be critical to oxidative stress homeostasis, thus shedding light on the relevance of the redox balance in the central nervous system integrity.
authors.affiliation: Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Signorini
authors.affiliation: Neonatal Intensive Care Unit, Azienda Ospedaliera Universitaria Senese, Siena, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: De Felice
authors.affiliation: Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy.|Child Neuropsychiatry Unit, Azienda Ospedaliera Universitaria Senese, Siena, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Leoncini
authors.affiliation: Danish Epilepsy Centre, Dianalund, Denmark.|Institute for Regional Health Services, University of Southern Denmark, Odense, Denmark.
authors.forename: Rikke S
authors.initials: RS
authors.lastname: Møller
authors.affiliation: Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy.|Child Neuropsychiatry Unit, Azienda Ospedaliera Universitaria Senese, Siena, Italy.
authors.forename: Gloria
authors.initials: G
authors.lastname: Zollo
authors.affiliation: Child Neuropsychiatry Unit, Azienda Ospedaliera Universitaria Senese, Siena, Italy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Buoni
authors.affiliation: Child Neuropsychiatry Unit, Azienda Ospedaliera Universitaria Senese, Siena, Italy.
authors.forename: Alessio
authors.initials: A
authors.lastname: Cortelazzo
authors.affiliation: Department of Medical Biotechnologies,University of Siena, Siena, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Guerranti
authors.affiliation: Institut des Biomolécules Max Mousseron (IBMM), UMR 5247-CNRS-UM-ENSCM, Montpellier, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Durand
authors.affiliation: Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Ciccoli
authors.affiliation: Institute of Genetics and Biophysics "A. Buzzati-Traverso", Naples, Italy.|IRCSS Neuromed, Pozzilli, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: D'Esposito
authors.affiliation: Department of Clinical Genetics, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: Kirstine
authors.initials: K
authors.lastname: Ravn
authors.affiliation: Child Neuropsychiatry Unit, Azienda Ospedaliera Universitaria Senese, Siena, Italy.
authors.forename: Joussef
authors.initials: J
authors.lastname: Hayek
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D028441:F2-Isoprostanes / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D038901:X-Linked Intellectual Disability / Q000235:genetics / Q000378:metabolism*; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D018384:Oxidative Stress / Q000235:genetics*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015518:Rett Syndrome / Q000235:genetics / Q000378:metabolism*
chemical_list: D028441:F2-Isoprostanes; D005227:Fatty Acids; D051783:Methyl-CpG-Binding Protein 2; D017382:Reactive Oxygen Species