Genes related to mitochondrial functions, protein degradation, and chromatin folding are differentially expressed in lymphomonocytes of Rett syndrome patients.
Rett syndrome (RTT) is mainly caused by mutations in the X-linked methyl-CpG binding protein (MeCP2) gene. By binding to methylated promoters on CpG islands, MeCP2 protein is able to modulate several genes and important cellular pathways. Therefore, mutations in MeCP2 can seriously affect the cellular phenotype. Today, the pathways that MeCP2 mutations are able to affect in RTT are not clear yet. The aim of our study was to investigate the gene expression profiles in peripheral blood lymphomonocytes (PBMC) isolated from RTT patients to try to evidence new genes and new pathways that are involved in RTT pathophysiology. LIMMA (Linear Models for MicroArray) and SAM (Significance Analysis of Microarrays) analyses on microarray data from 12 RTT patients and 7 control subjects identified 482 genes modulated in RTT, of which 430 were upregulated and 52 were downregulated. Functional clustering of a total of 146 genes in RTT identified key biological pathways related to mitochondrial function and organization, cellular ubiquitination and proteosome degradation, RNA processing, and chromatin folding. Our microarray data reveal an overexpression of genes involved in ATP synthesis suggesting altered energy requirement that parallels with increased activities of protein degradation. In conclusion, these findings suggest that mitochondrial-ATP-proteasome functions are likely to be involved in RTT clinical features.
Department of Molecular and Developmental Medicine, University of Siena, 53100 Siena, Italy ; Child Neuropsychiatry Unit, University Hospital, Azienda Ospedaliera Universitaria Senese, 53100 Siena, Italy.
Alessandra
A
Pecorelli
National Research Institute on Food and Nutrition (INRAN), 00178 Rome, Italy.
Guido
G
Leoni
Department of Life Science and Biotechnologies, University of Ferrara, 44121 Ferrara, Italy.
Franco
F
Cervellati
National Research Institute on Food and Nutrition (INRAN), 00178 Rome, Italy.
Raffaella
R
Canali
Department of Molecular and Developmental Medicine, University of Siena, 53100 Siena, Italy.
Cinzia
C
Signorini
Department of Molecular and Developmental Medicine, University of Siena, 53100 Siena, Italy ; Child Neuropsychiatry Unit, University Hospital, Azienda Ospedaliera Universitaria Senese, 53100 Siena, Italy.
Silvia
S
Leoncini
Child Neuropsychiatry Unit, University Hospital, Azienda Ospedaliera Universitaria Senese, 53100 Siena, Italy ; Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy.
Alessio
A
Cortelazzo
Neonatal Intensive Care Unit, University Hospital, Azienda Ospedaliera Universitaria Senese, 53100 Siena, Italy.
Claudio
C
De Felice
Department of Molecular and Developmental Medicine, University of Siena, 53100 Siena, Italy.
Lucia
L
Ciccoli
Child Neuropsychiatry Unit, University Hospital, Azienda Ospedaliera Universitaria Senese, 53100 Siena, Italy.
Joussef
J
Hayek
Department of Life Science and Biotechnologies, University of Ferrara, 44121 Ferrara, Italy ; Department of Food and Nutrition, Kyung Hee University, Seoul 130-701, Republic of Korea.
Giuseppe
G
Valacchi
D000255:Adenosine Triphosphate / Q000502:physiology; D000293:Adolescent; D000328:Adult; D002648:Child; D002843:Chromatin / Q000737:chemistry*; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics; D008928:Mitochondria / Q000502:physiology*; D018384:Oxidative Stress; D046988:Proteasome Endopeptidase Complex / Q000502:physiology; D059748:Proteolysis; D015518:Rett Syndrome / Q000235:genetics* / Q000378:metabolism; D059467:Transcriptome; D054875:Ubiquitination
D002843:Chromatin; C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2; D000255:Adenosine Triphosphate; D046988:Proteasome Endopeptidase Complex