As mentioned above, several mechanisms that have been proposed to explain the pathogenesis of FXTAS, including RNA toxicity, RAN translation producing the accumulation of the FMR PolyG polypeptide, and damage response, are linked to white-matter-tract connectivity in the brain, called white-matter hyperintensities, and strongly associated to the clinical impairment observed in FXTAS [6,28,148]. This evidence concerns the gene RAN and fragile X-associated tremor/ataxia syndrome.