FXS is one of the most common causes of syndromic autism, and often also causes moderate to severe intellectual disability, speech delays, growth and motor abnormalities, hyperactivity, and anxiety 93,94. FXS is thought to be the result of decreased expression of the FMR1 gene, which encodes FMRP, an RNA-binding protein that inhibits mRNA translation. Regulation of mRNA translation is thought to be important for synaptic plasticity and neuronal maturation, thus making this gene crucial for normal brain development. More specifically, expansion of CGG repeats in the 5′ UTR of the FMR1 gene results in hyper-methylation and consequent silencing of the gene in an X-linked dominant manner. Healthy individuals have ~6–40 CGG repeats in their FMR1 gene whereas affected individuals have >200–230 CGG repeats 95. Elevated protein synthesis at baseline as a consequence of FMR1 reduced expression leads to an absence in synaptic activity-dependent protein synthesis, which in turns disrupts several higher cognitive processes 96–98. Without synaptic activation-dependent protein synthesis, processes that are involved in the physical encoding of information storage in the brain circuitry cannot function fully.
