Transcriptional silencing contributes to the pathophysiology caused by large expansions of a CGG trinucleotide (over 200) in the 5′-UTR region of the fragile X mental retardation 1 gene (FMR1), leading to the Fragile X syndrome (FXS), the most common inherited form of intellectual disability, due to haploinsufficiency and loss of the FMRP protein, which plays a role in repressing the translation of specific mRNAs for synaptic plasticity in dendrites. This evidence concerns the gene FMR1 and fragile X syndrome.