Figure 2

Molecular overlap between autism, fragile x syndrome (FXS) and premutation disorders. Absence of the FMR1 protein (FMRP) leads to the dysregulation of several proteins including those involved with synapse formation and plasticity, glutamate and γ aminobuyric acid (GABA) neurotransmission and mammalian target of rapamycin (mTOR) and phosphatase and tensin homolog (PTEN) pathways. A premutation is associated with elevation of FMR1 mRNA, leading to sequestration of proteins and mitochondrial dysfunction. Many of these same molecular changes can also occur in some types of autism. Some patients with FXS have mosaicism of premutation and full cells, so there is overlap of the molecular mechanisms among all three disorders.