title: Intragenic inversion of mtDNA: a new type of pathogenic mutation in a patient with mitochondrial myopathy.
abstract: We report an unusual molecular defect in the mitochondrially encoded ND1 subunit of NADH ubiquinone oxidoreductase (complex I) in a patient with mitochondrial myopathy and isolated complex I deficiency. The mutation is an inversion of seven nucleotides within the ND1 gene, which maintains the reading frame. The inversion, which alters three highly conserved amino acids in the polypeptide, was heteroplasmic in the patient's muscle but was not detectable in blood. This is the first report of a pathogenic inversion mutation in human mtDNA.
authors.affiliation: H. Houston Merritt Center for Muscular Dystrophy and Related Diseases, Department of Neurology, Columbia University College of Physicians and Surgeons, New York, USA.
authors.forename: O
authors.initials: O
authors.lastname: Musumeci
authors.forename: A L
authors.initials: AL
authors.lastname: Andreu
authors.forename: S
authors.initials: S
authors.lastname: Shanske
authors.forename: N
authors.initials: N
authors.lastname: Bresolin
authors.forename: G P
authors.initials: GP
authors.lastname: Comi
authors.forename: R
authors.initials: R
authors.lastname: Rothstein
authors.forename: E A
authors.initials: EA
authors.lastname: Schon
authors.forename: S
authors.initials: S
authors.lastname: DiMauro
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D007446:Chromosome Inversion; D017124:Conserved Sequence / Q000235:genetics; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D042967:Electron Transport Complex I; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D017240:Mitochondrial Myopathies / Q000201:enzymology / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009247:NADH, NADPH Oxidoreductases / Q000172:deficiency / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D021122:Protein Subunits; D011995:Recombination, Genetic / Q000235:genetics
chemical_list: D004272:DNA, Mitochondrial; D021122:Protein Subunits; D009247:NADH, NADPH Oxidoreductases; D042967:Electron Transport Complex I