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. In this review the known changes in metabolite levels, gene expression and biological pathways in RTT are summarized. It is discussed how they are leading to some characteristic RTT phenotypes and identifies the gaps of knowledge, 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.