Intragenic inversion of mtDNA: A new type of pathogenic mutation in a patient with mitochondrial myopathy

We report an unusual molecular defect in the mitochondrially encoded ND1 su bunit of NADH ubiquinone oxidoreductase (complex I) in a patient with mitoc hondrial myopathy and isolated complex I deficiency. The mutation is an inv ersion of seven nucleotides within the ND1 gene, which maintains the readin g frame. The inversion, which alters three highly conserved amino acids in the polypeptide, was heteroplasmic in the patient's muscle but was not dete ctable in blood. This is the first report of a pathogenic inversion mutatio n in human mtDNA.