While we could not evaluate the role of MSH2 in establishing DNA methylation at the FMR1 locus in FXS ESCs, our results clearly show that MSH2 is not required for the maintenance of DNA methylation induced by repeat expansion in either FXS or FRDA, and that this difference from what is seen in DM1 cannot be attributed to the difference in the overall GC content or CpG density of the regions examined. This evidence concerns the gene MSH2 and fragile X syndrome.