RNA toxicity due to increased FMR1 mRNA levels observed in premutation carriers is the leading molecular mechanism proposed for FMR1 associated disorders. Our analysis comparing premutation carriers and control samples suggests that RNA toxicity may arise from increased expression levels of all FMR1 mRNA isoforms. In addition, Iso10 and Iso10b transcripts, which lack important functional sites for FMRP function encoded in the missing C-terminal, are the most differentially expressed in premutation carriers relative to controls, suggesting a potential functional relevance in the pathology of FMR1 associated premutation disorders. (By Dr. Dalyir Pretto, http://jmg.bmj.com/content/early/2014/10/30/jmedgenet-2014-102593 )