title: Exercise intolerance due to a nonsense mutation in the mtDNA ND4 gene.
abstract: We report the first molecular defect in an NADH-dehydrogenase gene presenting as isolated myopathy. The proband had lifelong exercise intolerance but no weakness. A muscle biopsy showed cytochrome c oxidase (COX)-positive ragged-red fibers (RRFs), and analysis of the mitochondrial enzymes revealed complex I deficiency. Sequence analysis of the mitochondrial genes encoding the seven NADH-dehydrogenase subunits showed a G-to-A transition at nucleotide 11832 in the subunit 4 (ND4) gene, which changed an encoded tryptophan to a stop codon. The mutation was heteroplasmic (54%) in muscle DNA. Defects in mitochondrially encoded complex I subunits should be added to the differential diagnosis of mitochondrial myopathies.
authors.affiliation: H. Houston Merritt Center for Muscular Dystrophy and Related Diseases, Department of Neurology, Columbia College of Physicians and Surgeons, New York, NY 10032, USA.
authors.forename: A L
authors.initials: AL
authors.lastname: Andreu
authors.forename: K
authors.initials: K
authors.lastname: Tanji
authors.forename: C
authors.initials: C
authors.lastname: Bruno
authors.forename: G M
authors.initials: GM
authors.lastname: Hadjigeorgiou
authors.forename: C M
authors.initials: CM
authors.lastname: Sue
authors.forename: C
authors.initials: C
authors.lastname: Jay
authors.forename: T
authors.initials: T
authors.lastname: Ohnishi
authors.forename: S
authors.initials: S
authors.lastname: Shanske
authors.forename: E
authors.initials: E
authors.lastname: Bonilla
authors.forename: S
authors.initials: S
authors.lastname: DiMauro
mesh_terms: D000328:Adult; D004272:DNA, Mitochondrial / Q000032:analysis*; D015444:Exercise / Q000502:physiology*; D006801:Humans; D008297:Male; D009135:Muscular Diseases / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology*; D009154:Mutation / Q000235:genetics; D009245:NADH Dehydrogenase / Q000235:genetics*
chemical_list: D004272:DNA, Mitochondrial; D009245:NADH Dehydrogenase