Rett syndrome is a complex neuropsychiatric disorder characterized by motor disturbances, mental retardation, and epilepsy, as well as developmental regression and the appearance of autistic features. X-linked, Rett syndrome almost exclusively affects girls and in nearly all cases arises from a mutation in the gene MeCP2. The disorder’s broad nature is likely due to the fact that MeCP2 acts in part as a transcriptional repressor that binds to methylated CpG islands on DNA. Bound to DNA, MeCP2 can recruit histone-deacetylase (HDAC) to modify chromatin structure, blocking transcription. MeCP2 has also been shown to bind to other genomic sites as well as to microRNA, suggesting other modes of action. Studying Rett syndrome is strongly clinically relevant, in that 1:10,000 girls and their families are effected by this developmental disorder. Scientifically, Rett syndrome is a particularly interesting neuropsychiatry disease: it has a clear epigenetic etiology, affecting a number of important genes implicated in learning and memory, neuronal development, schizophrenia, autism, epilepsy, and depression. Therefore, as well as focusing on clinically important disease, work in models of Rett syndrome cuts across many more common neuropsychiatry disorders. This work also implicates basic neuroscience questions that query the role of epigenetic modifications in development, imprinting, and neuronal morphology and connectivity, as well as in learning and memory.
Information for families and further information about research in Rett syndrome can be found at the International Rett Syndrome Foundation (IRSF: http://www.rettsyndrome.org/). IRSF is a generous supporter of Rett syndrome research at the CNB.
Investigators involved in this area: