We detected a novel frameshift mutation predicted to prematurely truncate the p53R2 protein by introducing a stop codon 11 amino acids downstream in the ribonucleotide reductase domain of RRM2B in two unrelated subjects with molecular evidence of MDS, including reduced mtDNA copy number and depressed activity for the mtDNA dependent RC complexes. The gene discussed is RRM2B; the disease is myelodysplastic syndrome.