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 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.
Andreu
A L
AL
H. Houston Merritt Center for Muscular Dystrophy and Related Diseases, Department of Neurology, Columbia College of Physicians and Surgeons, New York, NY 10032, USA.
Tanji
K
K
Bruno
C
C
Hadjigeorgiou
G M
GM
Sue
C M
CM
Jay
C
C
Ohnishi
T
T
Shanske
S
S
Bonilla
E
E
DiMauro
S
S
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*
D004272:DNA, Mitochondrial; D009245:NADH Dehydrogenase