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

A. L. Andreu, K. Tanji, C. Bruno, G. M. Hadjigeorgiou, C. M. Sue, C. Jay, T. Ohnishi, S. Shanske, E. Bonilla, S. DiMauro

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)820-823
Number of pages4
JournalAnnals of Neurology
Issue number6
Publication statusPublished - 1999

ASJC Scopus subject areas

  • Neuroscience(all)


Dive into the research topics of 'Exercise intolerance due to a nonsense mutation in the mtDNA ND4 gene'. Together they form a unique fingerprint.

Cite this