A plasma proteomic approach in Rett syndrome: classical versus preserved speech variant.
Rett syndrome (RTT) is a progressive neurodevelopmental disorder mainly caused by mutations in the gene encoding the methyl-CpG-binding protein 2 (MeCP2). Although over 200 mutations types have been identified so far, nine of which the most frequent ones. A wide phenotypical heterogeneity is a well-known feature of the disease, with different clinical presentations, including the classical form and the preserved speech variant (PSV). Aim of the study was to unveil possible relationships between plasma proteome and phenotypic expression in two cases of familial RTT represented by two pairs of sisters, harbor the same MECP2 gene mutation while being dramatically discrepant in phenotype, that is, classical RTT versus PSV. Plasma proteome was analysed by 2-DE/MALDI-TOF MS. A significant overexpression of six proteins in the classical sisters was detected as compared to the PSV siblings. A total of five out of six (i.e., 83.3%) of the overexpressed proteins were well-known acute phase response (APR) proteins, including alpha-1-microglobulin, haptoglobin, fibrinogen beta chain, alpha-1-antitrypsin, and complement C3. Therefore, the examined RTT siblings pairs proved to be an important benchmark model to test the molecular basis of phenotypical expression variability and to identify potential therapeutic targets of the disease.
Department of Medical Biotechnologies, University of Siena, Via A. Moro 2, 53100 Siena, Italy ; Child Neuropsychiatry Unit, University Hospital Azienda Ospedaliera Universitaria Senese (AOUS), Viale M. Bracci 16, 53100 Siena, Italy.
Alessio
A
Cortelazzo
Department of Medical Biotechnologies, University of Siena, Via A. Moro 2, 53100 Siena, Italy.
Roberto
R
Guerranti
Neonatal Intensive Care Unit, University Hospital AOUS, Viale M. Bracci 16, 53100 Siena, Italy.
Claudio
C
De Felice
Department of Molecular and Developmental Medicine, University of Siena, Via A. Moro 6, 53100 Siena, Italy.
Cinzia
C
Signorini
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.
Silvia
S
Leoncini
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.
Alessandra
A
Pecorelli
Department of Life Science, University of Siena, Via A. Moro 2, 53100 Siena, Italy.
Claudia
C
Landi
Department of Life Science, University of Siena, Via A. Moro 2, 53100 Siena, Italy.
Luca
L
Bini
Child Neuropsychiatry Unit, University Hospital Azienda Ospedaliera Universitaria Senese (AOUS), Viale M. Bracci 16, 53100 Siena, Italy.
Barbara
B
Montomoli
Department of Life Sciences and Biotechnology, University of Ferrara, Via Borsari 46, 44100 Ferrara, Italy.
Claudia
C
Sticozzi
Department of Molecular and Developmental Medicine, University of Siena, Via A. Moro 6, 53100 Siena, Italy.
Lucia
L
Ciccoli
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.
Giuseppe
G
Valacchi
Child Neuropsychiatry Unit, University Hospital Azienda Ospedaliera Universitaria Senese (AOUS), Viale M. Bracci 16, 53100 Siena, Italy.
Joussef
J
Hayek
D000210:Acute-Phase Reaction; D000328:Adult; D001798:Blood Proteins / Q000032:analysis*; D005260:Female; D006801:Humans; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics; D010641:Phenotype; D040901:Proteomics / Q000379:methods*; D015518:Rett Syndrome / Q000097:blood* / Q000145:classification / Q000235:genetics; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D001798:Blood Proteins; C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2