Early linkage analyses and recent genome-wide association studies with exome sequencing revealed pathogenic mutations in mt-tRNA-modifying enzymes associated with specific disorders; PUS1 in mitochondrial myopathy and sideroblastic anemia29; MTU1 in acute infantile liver failure30–33; GTPBP3 in hypertrophic cardiomyopathy, lactic acidosis, and encephalopathy or Leigh syndrome34,35; MTO1 in hypertrophic cardiomyopathy and lactic acidosis36–38; TRIT1 in encephalopathy and myoclonic epilepsy39; and NSUN3 in combined mitochondrial respiratory chain complex deficiency27. This evidence concerns the gene GTPBP3 and lactic acidosis.