It is also worth of note that FXTAS and FXPOI are never observed in FXS patients, since the underlying mechanism is different: FM alleles are silenced and both FMR1 mRNA and FMRP are lacking (loss-of-function), while PM alleles are transcribed and the expanded CGG repeat in the 5′ untranslated region of the mRNA causes neurodegeneration with at least two gain-of-function mechanisms, namely, RNA toxicity and production of abnormal polypeptides due to repeat-associated non-AUG (RAN)-dependent translation [22]. This evidence concerns the gene FMR1 and fragile X syndrome.