The inherited neurodegenerative disease Friedreich’s ataxia (FRDA) is caused by hyperexpansion of GAA•TTC trinucleotide repeats within the first intron of the FXN gene, encoding the mitochondrial protein frataxin. Long GAA•TTC repeats causes heterochromatin-mediated silencing and loss of frataxin in affected individuals. We report the derivation of induced pluripotent stem cells (iPSCs) from FRDA patient fibroblasts through retroviral transduction of transcription factors. FXN gene repression is maintained in the iPSCs, as are the mRNA and miRNA global expression signatures reflecting the human disease. GAA•TTC repeats uniquely in FXN in the iPSCs exhibit repeat instability similar to patient families, where they expand and/or contract with discrete changes in length between generations. The mismatch repair enzyme Msh2, implicated in repeat instability in other triplet repeat diseases, is highly expressed in the iPSCs, occupies FXN intron 1, and shRNA silencing of Msh2 impedes repeat expansion, providing a possible molecular explanation for repeat expansion in FRDA. Overall design: 65 samples from various number of tissue, primary cell lines undifferenatiated human embryonic stem cell lines, induces pluripotent stem cell lines have been run on Illumina HT12 v3 chips.