Year: 2013
Type: dissertation
Abstract: Objective: The aim of this review is to investigate the two syndromes Rett syndrome (RTT) and MECP2 duplication syndrome (MECP2ds), with emphasis on phenotypic traits that are shared by the two syndromes. Additional goals is to explore the role of the MeCP2 protein in an epigenetic context, and in the pathogenesis of the two syndromes. Finally I will look at the future prospects of finding treatments for the two syndromes that extend beyond conservative reliever therapy. Background: RTT and MECP2ds are both neurological disorders related to faulty X chromosome, which both provide developmental disorders. RTT targets females and is caused by a deletion of the MECP2 gene encoding the methyl-CpG-binding protein 2 (MeCP2), and thus loss of function of the protein. MECP2ds almost exclusively affects males and is caused by a duplication of the MECP2 gene, leading to gain of function of the MeCP2 protein. Nevertheless the two syndromes show a noteworthy number of similar phenotypic characteristics. Method: Literature searches including both review articles and original publications in McMaster Plus, PubMed/Medline, Ovid, Cochrane, and Google Scholar. Only articles written in english or norwegian were included. Searches were based on relevant keywords focused on the genetic and clinical aspects of RTT and MECP2ds, correlation between the two syndromes and the MeCP2 protein, the epigenetic aspect of the MeCP2 protein, as well as the more recent publications regarding treatment. Result and Conclusion: Despite a great deal of differences between RTT and MECP2ds, there are remarkably many similarities in the phenotypic expression shown by the two syndromes, such as aberrant psychomotor development and motor dysfunction, regression, reduced or absent speech and walking ability, ataxia and spasticity, autism, stereotypical movements, epilepsy and gastrointestinal dysfunction. The MeCP2 protein is a transcription factor that controls gene expression, and is a key epigenetic factor in development and maintenance of the central nervous system. Common features of neurological diseases in humans which are caused by either loss or increased MeCP2 function, suggest that even small changes in the level of MeCP2 protein results in developmental neurological problems. There is intense research in the field to find gene therapy and various drugs as potential treatments for diseases related to disorders of the MeCP2 protein. Gene therapy has shown some promising results in vitro using retroviral vectors. Medications such as IGF1 and Gentamicin may be promising as a therapy directed at early stages of development in RTT, as they may reduce the consequences of MECP2 mutations. But to restore the protein levels remains a great challenge, since an excess of MeCP2 can be just as damaging as the loss of expression. Clinical trials are not currently within reach. Considering MECP2ds it is also necessary to facilitate research on the molecular background of immunodeficiency, which is a major cause of premature death in this patient population.
Author: Silje Madeleine Kalstø
Language: Norwegian
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2278137794