Exercise intolerance due to a nonsense mutation in the mtDNA ND4 gene
A. L. Andreu MD
H. Houston Merritt Center for Muscular Dystrophy and Related Diseases, Department of Neurology, Columbia College of Physicians and Surgeons, New York, NY
Centre d'Investigacions en Bioquimica i Biologia Molecular, Hospitals Vall d'Hebron, Barcelona, Spain
Search for more papers by this authorK. Tanji MD
H. Houston Merritt Center for Muscular Dystrophy and Related Diseases, Department of Neurology, Columbia College of Physicians and Surgeons, New York, NY
Search for more papers by this authorC. Bruno MD
H. Houston Merritt Center for Muscular Dystrophy and Related Diseases, Department of Neurology, Columbia College of Physicians and Surgeons, New York, NY
Servizio Malattie Neuromuscolari, Department of Pediatrics, University of Genoa, Istituto Giannina Gaslini, Genoa, Italy
Search for more papers by this authorG. M. Hadjigeorgiou MD, PhD
H. Houston Merritt Center for Muscular Dystrophy and Related Diseases, Department of Neurology, Columbia College of Physicians and Surgeons, New York, NY
Search for more papers by this authorC. M. Sue MD, PhD
H. Houston Merritt Center for Muscular Dystrophy and Related Diseases, Department of Neurology, Columbia College of Physicians and Surgeons, New York, NY
Search for more papers by this authorC. Jay MD
University of California, San Francisco, Department of Neurology, San Francisco General Hospital, San Francisco, CA
Search for more papers by this authorT. Ohnishi PhD
Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, PA
Search for more papers by this authorS. Shanske PhD
H. Houston Merritt Center for Muscular Dystrophy and Related Diseases, Department of Neurology, Columbia College of Physicians and Surgeons, New York, NY
Search for more papers by this authorE. Bonilla MD
H. Houston Merritt Center for Muscular Dystrophy and Related Diseases, Department of Neurology, Columbia College of Physicians and Surgeons, New York, NY
Search for more papers by this authorCorresponding Author
S. DiMauro MD
H. Houston Merritt Center for Muscular Dystrophy and Related Diseases, Department of Neurology, Columbia College of Physicians and Surgeons, New York, NY
Department of Neurology, 4-420 College of Physicians and Surgeons, 630 West 168th Street, New York, NY 10032Search for more papers by this authorA. L. Andreu MD
H. Houston Merritt Center for Muscular Dystrophy and Related Diseases, Department of Neurology, Columbia College of Physicians and Surgeons, New York, NY
Centre d'Investigacions en Bioquimica i Biologia Molecular, Hospitals Vall d'Hebron, Barcelona, Spain
Search for more papers by this authorK. Tanji MD
H. Houston Merritt Center for Muscular Dystrophy and Related Diseases, Department of Neurology, Columbia College of Physicians and Surgeons, New York, NY
Search for more papers by this authorC. Bruno MD
H. Houston Merritt Center for Muscular Dystrophy and Related Diseases, Department of Neurology, Columbia College of Physicians and Surgeons, New York, NY
Servizio Malattie Neuromuscolari, Department of Pediatrics, University of Genoa, Istituto Giannina Gaslini, Genoa, Italy
Search for more papers by this authorG. M. Hadjigeorgiou MD, PhD
H. Houston Merritt Center for Muscular Dystrophy and Related Diseases, Department of Neurology, Columbia College of Physicians and Surgeons, New York, NY
Search for more papers by this authorC. M. Sue MD, PhD
H. Houston Merritt Center for Muscular Dystrophy and Related Diseases, Department of Neurology, Columbia College of Physicians and Surgeons, New York, NY
Search for more papers by this authorC. Jay MD
University of California, San Francisco, Department of Neurology, San Francisco General Hospital, San Francisco, CA
Search for more papers by this authorT. Ohnishi PhD
Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, PA
Search for more papers by this authorS. Shanske PhD
H. Houston Merritt Center for Muscular Dystrophy and Related Diseases, Department of Neurology, Columbia College of Physicians and Surgeons, New York, NY
Search for more papers by this authorE. Bonilla MD
H. Houston Merritt Center for Muscular Dystrophy and Related Diseases, Department of Neurology, Columbia College of Physicians and Surgeons, New York, NY
Search for more papers by this authorCorresponding Author
S. DiMauro MD
H. Houston Merritt Center for Muscular Dystrophy and Related Diseases, Department of Neurology, Columbia College of Physicians and Surgeons, New York, NY
Department of Neurology, 4-420 College of Physicians and Surgeons, 630 West 168th Street, New York, NY 10032Search for more papers by this authorAbstract
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
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