We further show that pharmacological reactivation of the FMR1 locus results in expression of mis-spliced transcripts and that FMRP loss alone, in the absence of an expanded CGG tract, causes only a modest increase in splicing defect.<h4>Conclusions</h4>These results suggest that mis-splicing may represent one of several mechanisms contributing to the absence of FMRP in FXS, specifically in cases where transcriptional silencing of the FMR1 locus is incomplete and expanded transcripts are still produced. This evidence concerns the gene FMR1 and fragile X syndrome.