title: Rett syndrome - biological pathways leading from MECP2 to disorder phenotypes.
abstract: Rett syndrome (RTT) is a rare disease but still one of the most abundant causes for intellectual disability in females. Typical symptoms are onset at month 6-18 after normal pre- and postnatal development, loss of acquired skills and severe intellectual disability. The type and severity of symptoms are individually highly different. A single mutation in one gene, coding for methyl-CpG-binding protein 2 (MECP2), is responsible for the disease. The most important action of MECP2 is regulating epigenetic imprinting and chromatin condensation, but MECP2 influences many different biological pathways on multiple levels although the molecular pathways from gene to phenotype are currently not fully understood. In this review the known changes in metabolite levels, gene expression and biological pathways in RTT are summarized, discussed how they are leading to some characteristic RTT phenotypes and therefore the gaps of knowledge are identified. Namely, which phenotypes have currently no mechanistic explanation leading back to MECP2 related pathways? As a result of this review the visualization of the biologic pathways showing MECP2 up- and downstream regulation was developed and published on WikiPathways which will serve as template for future omics data driven research. This pathway driven approach may serve as a use case for other rare diseases, too.
authors.affiliation: Governor Kremers Centre - Rett Expertise Centre, Maastricht University Medical Center, Maastricht, The Netherlands. friederike.ehrhart@maastrichtuniversity.nl.|Department of Bioinformatics, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands. friederike.ehrhart@maastrichtuniversity.nl.
authors.forename: Friederike
authors.identifier: 0000-0002-7770-620X
authors.initials: F
authors.lastname: Ehrhart
authors.affiliation: Department of Bioinformatics, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands.
authors.forename: Susan L M
authors.initials: SL
authors.lastname: Coort
authors.affiliation: Department of Bioinformatics, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands.
authors.forename: Elisa
authors.initials: E
authors.lastname: Cirillo
authors.affiliation: Governor Kremers Centre - Rett Expertise Centre, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Eric
authors.initials: E
authors.lastname: Smeets
authors.affiliation: Governor Kremers Centre - Rett Expertise Centre, Maastricht University Medical Center, Maastricht, The Netherlands.|Department of Bioinformatics, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands.
authors.forename: Chris T
authors.initials: CT
authors.lastname: Evelo
authors.affiliation: Governor Kremers Centre - Rett Expertise Centre, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Leopold M G
authors.initials: LM
authors.lastname: Curfs
mesh_terms: D000818:Animals; D019295:Computational Biology; D019175:DNA Methylation / Q000235:genetics; D004195:Disease Models, Animal; D057890:Epigenomics; D006801:Humans; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics / Q000378:metabolism*; D015518:Rett Syndrome / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D049490:Systems Biology
chemical_list: D051783:Methyl-CpG-Binding Protein 2
keywords: Bioinformatics; DNA methylation; Data integration; Epigenetics; MECP2; Rett syndrome; Systems biology