title: F₄-neuroprostanes mediate neurological severity in Rett syndrome.
abstract: BACKGROUND
  Rett syndrome (RTT) is a pervasive development disorder, mainly caused by mutations in the methyl-CpG binding protein 2 (MeCP2) gene. No reliable biochemical markers of the disease are available. Here we assess F₄-neuroprostanes (F₄-NeuroPs), lipid peroxidation products of the docosahexaenoic acid, as a novel disease marker in RTT and correlate it with clinical presentation, MeCP2 mutation type, and disease progression. In addition, we investigate on the impact of ω-3 polyunsaturated fatty acids (ω-3 PUFAs) supplementation on F₄-NeuroPs levels.
  
  
  METHODS
  A case-control study design was used. A cohort of RTT patients (n=144) exhibiting different clinical presentations, disease stages, and MeCP2 gene mutations were evaluated. F₄-NeuroPs were measured in free form using a GC/NICI-MS/MS technique. Plasma F₄-NeuroPs levels in patients were compared to healthy controls and related to RTT forms, disease progression, and response to ω-3 PUFAs supplementation.
  
  
  RESULTS
  Plasma F₄-NeuroPs levels were i) higher in RTT than in controls; ii) increased with the severity of neurological symptoms; iii) significantly elevated during the typical disease progression; iv) higher in MeCP2-nonsense as compared to missense mutation carriers; v) higher in typical RTT as compared to RTT variants; and vi) decreased in response to 12 months ω-3 PUFAs oral supplementation.
  
  
  CONCLUSIONS
  Quantification of plasma F₄-NeuroPs provides a novel RTT marker, related to neurological symptoms severity, mutation type and clinical presentation.
authors.affiliation: Department of Pathophysiology, Experimental Medicine & Public Health, University of Siena, Siena, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Signorini
authors.forename: Claudio
authors.initials: C
authors.lastname: De Felice
authors.forename: Silvia
authors.initials: S
authors.lastname: Leoncini
authors.forename: Anna
authors.initials: A
authors.lastname: Giardini
authors.forename: Maurizio
authors.initials: M
authors.lastname: D'Esposito
authors.forename: Stefania
authors.initials: S
authors.lastname: Filosa
authors.forename: Floriana
authors.initials: F
authors.lastname: Della Ragione
authors.forename: Marcello
authors.initials: M
authors.lastname: Rossi
authors.forename: Alessandra
authors.initials: A
authors.lastname: Pecorelli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Valacchi
authors.forename: Lucia
authors.initials: L
authors.lastname: Ciccoli
authors.forename: Joussef
authors.initials: J
authors.lastname: Hayek
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D028421:Isoprostanes / Q000097:blood*; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics; D009154:Mutation; D009460:Neurologic Examination; D015518:Rett Syndrome / Q000097:blood* / Q000175:diagnosis; D055815:Young Adult
chemical_list: D015415:Biomarkers; D028421:Isoprostanes; C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2