Fragile X syndrome : An epigenetic disease

In fragile X syndrome the protein product of the FMR1 gene (FMRP) is missing and this causes the disease phenotype. Actually the coding sequence of the FMR1 gene is not changed, but a CGG repeat in the 5' UTR of gene is expanded. As a consequence the repeat and promoter of the FMR1 gene become hypermethylated, which leads to silencing of the gene. Because ofthis fragile X syndrome has been classified among the epigenetic diseases . In this chapter the different aspects of epigenetics of the FMRI gene are discussed. A brief description of the FMRI promoter and its transcription binding sites is given and the mechanisms of expansion of the CGG repeat and its effect on transcription and translation are discussed. The silencing of the FMRI gene, which occurs via methylation and his tone modifications, as well as the reactivation approaches applied so far are summarized. Finally the regulatory role of FMRP and the latest discoveries of its involvement in the RNAi pathway are described.