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Cited by 69Genetics and Neurodevelopmental DisordersChild Nutrition and Feeding IssuesAutism Spectrum Disorder Research

Oxidative stress in Rett syndrome: natural history, genotype, and variants

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Leoncini, Silvia, De Felice, Claudio, Signorini, Cinzia, Pecorelli, Alessandra, Durand, Thierry, Valacchi, Giuseppe, Ciccoli, Lucia, Hayek, Joussef·2011·Redox Report
DOI 10.1179/1351000211y.0000000004PMC PMC6837451
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Abstract

OBJECTIVES: Rett syndrome (RTT) is an X-linked autism spectrum disorder caused by mutations in the MeCP2 gene in the great majority of cases. Evidence suggests a potential role of oxidative stress (OS) in its pathogenesis. Here, we investigated the potential value of OS markers (non-protein-bound iron (NPBI) and F2-isoprostanes (F2-IsoPs)) in explaining natural history, genotype-phenotype correlation, and clinical heterogeneity of RTT, and gauging the response to omega-3 polyunsaturated fatty acids (ω-3 PUFAs). METHODS: RTT patients (n=113) and healthy controls were assayed for plasma NPBI and F2-IsoPs, and intraerythrocyte NPBI. Forty-two patients with typical RTT were randomly assigned to ω-3 PUFAs supplementation for 12 months. NPBI was measured by HPLC and F2-IsoPs using a gas chromatography/negative ion chemical ionization tandem mass spectrometry (GC/NICI-MS/MS) technique. RESULTS: F2-IsoPs were significantly higher in the early stages as compared with the late natural progression of classic RTT. MeCP2 mutations related to more severe phenotypes exhibited higher OS marker levels than those of milder phenotypes. Higher OS markers were observed in typical RTT and early seizure variant as compared with the preserved speech and congenital variants. Significant reduction in OS markers levels and improvement of severity scores were observed after ω-3 PUFAs supplementation. DISCUSSION: OS is a key modulator of disease expression in RTT.

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  • Increased oxidative stress has been observed in RTT patients.

    “Consistently, altered electron transport chain complex function [27], increased oxidative stress [28–30], and elevated levels of lactate and pyruvate in blood and cerebrospinal fluid [20,27] have been observed in RTT patients (reviewed in [31]).”

    From Rett syndrome: a neurological disorder with metabolic components (2018) · cites this paper as [30]

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Cited by

Sorted by citations

Authors
Leoncini, S., De Felice, C., Signorini, C., Pecorelli, A., Durand, T., Valacchi, G., Ciccoli, L., & Hayek, J.
Affiliations
  • University of Siena (IT)
  • Centre National de la Recherche Scientifique (FR)
  • University of Ferrara (IT)
ORCID
Venue
Redox Report
Publisher
Informa UK Limited
Published
2011-07
Volume
16
Issue
4
Pages
145-153
ISSN
  • 1351-0002 (ISSN-L)
  • 1743-2928
DOI
10.1179/1351000211y.0000000004
PMC
PMC6837451
OpenAlex
W2086670151
Cited by
69
References
4
Citations by year
2025: 2 · 2024: 5 · 2023: 2 · 2022: 3 · 2021: 2 · 2020: 2 · 2019: 3 · 2018: 5 · 2017: 6 · 2016: 5 · 2015: 5 · 2014: 10 · 2013: 12 · 2012: 5
FWCI
5.59
Type
journal article
Language
en
Open access
Locations
  • Redox Report (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Institutional Research Information System University of Ferrara (University of Ferrara) (submittedVersion)
  • Use Siena air (University of Siena) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Health Sciences › Medicine › Psychiatry and Mental health › Child Nutrition and Feeding Issues
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
Keywords
Rett syndrome, oxidative stress, MECP2 mutations, non-protein-bound iron, F2-isoprostanes, omega-3 polyunsaturated fatty acids, genotype-phenotype correlation, natural history (disease), clinical heterogeneity, disease severity, autism spectrum disorder
MeSH terms
Adolescent, Adult, Child, Child, Preschool, Female, Genotype, Humans, Mutation, Phenotype, Rett Syndrome, Fatty Acids, Omega-3, Oxidative Stress, Disease Progression, F2-Isoprostanes, Methyl-CpG-Binding Protein 2, Tandem Mass Spectrometry, Genetic Association Studies

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