Details

Autor(en) / Beteiligte

• Signorini, Cinzia
• De Felice, Claudio
• Leoncini, Silvia
• Møller, Rikke S
• Zollo, Gloria
• Buoni, Sabrina
• Cortelazzo, Alessio
• Guerranti, Roberto
• Durand, Thierry
• Ciccoli, Lucia
• D'Esposito, Maurizio
• Ravn, Kirstine
• Hayek, Joussef
• Colak, Dilek

Titel

MECP2 Duplication Syndrome: Evidence of Enhanced Oxidative Stress. A Comparison with Rett Syndrome

Ist Teil von

• PloS one, 2016-03, Vol.11 (3), p.e0150101-e0150101

Ort / Verlag

United States: Public Library of Science

Erscheinungsjahr

2016

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.