title: Subclinical inflammatory status in Rett syndrome.
abstract: Inflammation has been advocated as a possible common central mechanism for developmental cognitive impairment. Rett syndrome (RTT) is a devastating neurodevelopmental disorder, mainly caused by de novo loss-of-function mutations in the gene encoding MeCP2. Here, we investigated plasma acute phase response (APR) in stage II (i.e., "pseudo-autistic") RTT patients by routine haematology/clinical chemistry and proteomic 2-DE/MALDI-TOF analyses as a function of four major MECP2 gene mutation types (R306C, T158M, R168X, and large deletions). Elevated erythrocyte sedimentation rate values (median 33.0 mm/h versus 8.0 mm/h, P < 0.0001) were detectable in RTT, whereas C-reactive protein levels were unchanged (P = 0.63). The 2-DE analysis identified significant changes for a total of 17 proteins, the majority of which were categorized as APR proteins, either positive (n = 6 spots) or negative (n = 9 spots), and to a lesser extent as proteins involved in the immune system (n = 2 spots), with some proteins having overlapping functions on metabolism (n = 7 spots). The number of protein changes was proportional to the severity of the mutation. Our findings reveal for the first time the presence of a subclinical chronic inflammatory status related to the "pseudo-autistic" phase of RTT, which is related to the severity carried by the MECP2 gene mutation.
authors: Child Neuropsychiatry Unit, University Hospital Azienda Ospedaliera Universitaria Senese (AOUS), Viale M. Bracci 16, 53100 Siena, Italy ; Department of Medical Biotechnologies, University of Siena, Via A. Moro 2, 53100 Siena, Italy.
authors: Alessio
authors: A
authors: Cortelazzo
authors: Neonatal Intensive Care Unit, University Hospital AOUS, Viale M. Bracci 16, 53100 Siena, Italy.
authors: Claudio
authors: C
authors: De Felice
authors: Department of Medical Biotechnologies, University of Siena, Via A. Moro 2, 53100 Siena, Italy.
authors: Roberto
authors: R
authors: Guerranti
authors: Department of Molecular and Developmental Medicine, University of Siena, Via A. Moro 6, 53100 Siena, Italy.
authors: Cinzia
authors: C
authors: Signorini
authors: Child Neuropsychiatry Unit, University Hospital Azienda Ospedaliera Universitaria Senese (AOUS), Viale M. Bracci 16, 53100 Siena, Italy ; Department of Molecular and Developmental Medicine, University of Siena, Via A. Moro 6, 53100 Siena, Italy.
authors: Silvia
authors: S
authors: Leoncini
authors: Child Neuropsychiatry Unit, University Hospital Azienda Ospedaliera Universitaria Senese (AOUS), Viale M. Bracci 16, 53100 Siena, Italy ; Department of Molecular and Developmental Medicine, University of Siena, Via A. Moro 6, 53100 Siena, Italy.
authors: Alessandra
authors: A
authors: Pecorelli
authors: Child Neuropsychiatry Unit, University Hospital Azienda Ospedaliera Universitaria Senese (AOUS), Viale M. Bracci 16, 53100 Siena, Italy ; Department of Molecular and Developmental Medicine, University of Siena, Via A. Moro 6, 53100 Siena, Italy.
authors: Gloria
authors: G
authors: Zollo
authors: Department of Life Science, University of Siena, Via A. Moro 2, 53100 Siena, Italy.
authors: Claudia
authors: C
authors: Landi
authors: Department of Life Sciences and Biotechnology, University of Ferrara, Via Borsari 46, 44100 Ferrara, Italy ; Department of Food and Nutrition, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
authors: Giuseppe
authors: G
authors: Valacchi
authors: Department of Molecular and Developmental Medicine, University of Siena, Via A. Moro 6, 53100 Siena, Italy.
authors: Lucia
authors: L
authors: Ciccoli
authors: Department of Life Science, University of Siena, Via A. Moro 2, 53100 Siena, Italy.
authors: Luca
authors: L
authors: Bini
authors: Child Neuropsychiatry Unit, University Hospital Azienda Ospedaliera Universitaria Senese (AOUS), Viale M. Bracci 16, 53100 Siena, Italy.
authors: Joussef
authors: J
authors: Hayek
mesh_terms: D000210:Acute-Phase Reaction; D001799:Blood Sedimentation; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D025941:Protein Interaction Mapping; D015518:Rett Syndrome / Q000235:genetics* / Q000276:immunology*
chemical_list: C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2; D002097:C-Reactive Protein