Exercise intolerance due to a nonsense mutation in the mtDNA ND4 gene

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 c...

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Bibliographic Details
Published in:Annals of neurology 1999-06, Vol.45 (6), p.820-823
Main Authors: Andreu, A. L., Tanji, K., Bruno, C., Hadjigeorgiou, G. M., Sue, C. M., Jay, C., Ohnishi, T., Shanske, S., Bonilla, E., DiMauro, S.
Format: Article
Language:English
Subjects:
Adult
Biological and medical sciences
Diseases of striated muscles. Neuromuscular diseases
DNA, Mitochondrial - analysis
Exercise - physiology
Humans
Male
Medical sciences
Muscular Diseases - genetics
Muscular Diseases - metabolism
Muscular Diseases - physiopathology
Mutation - genetics
NADH Dehydrogenase - genetics
Neurology
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Summary: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. Ann Neurol 1999;45:820–823
ISSN:0364-5134
1531-8249
DOI:10.1002/1531-8249(199906)45:6<820::AID-ANA22>3.0.CO;2-W