Multiple mitochondrial DNA deletions in sporadic inclusion body myositis: A study of 56 patients

Authors

  • F. M. Santorelli MD,

    1. H. Houston Merritt Clinical Research Center for Muscular Dystrophy and Related Diseases-Departments of Neurology, Columbia University, New york, NY
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  • M. Sciacco MD,

    1. H. Houston Merritt Clinical Research Center for Muscular Dystrophy and Related Diseases-Departments of Neurology, Columbia University, New york, NY
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  • K. Tanji MD,

    1. H. Houston Merritt Clinical Research Center for Muscular Dystrophy and Related Diseases-Departments of Neurology, Columbia University, New york, NY
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  • S. Shanske PhD,

    1. H. Houston Merritt Clinical Research Center for Muscular Dystrophy and Related Diseases-Departments of Neurology, Columbia University, New york, NY
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  • T. H. Vu MD,

    1. H. Houston Merritt Clinical Research Center for Muscular Dystrophy and Related Diseases-Departments of Neurology, Columbia University, New york, NY
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  • V. Golzi MD,

    1. H. Houston Merritt Clinical Research Center for Muscular Dystrophy and Related Diseases-Departments of Neurology, Columbia University, New york, NY
    2. H. Houston Merritt Clinical Research Center for Muscular Dystrophy and Related Diseases-Neurological Institute H. S. Raffaele, Milan, Italy
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  • R. C. Griggs MD,

    1. H. Houston Merritt Clinical Research Center for Muscular Dystrophy and Related Diseases-Department Neurology, University of Rochester, Rochester, NY
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  • J. R. Mendell MD,

    1. H. Houston Merritt Clinical Research Center for Muscular Dystrophy and Related Diseases-Department of Neurology, Ohio State University, Columbus, OH
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  • A. P. Hays MD,

    1. H. Houston Merritt Clinical Research Center for Muscular Dystrophy and Related Diseases-Pathology, Columbia University, New york, NY
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  • T. E. Bertorini MD,

    1. H. Houston Merritt Clinical Research Center for Muscular Dystrophy and Related Diseases-Department of Neurology, University of Tennessee, Memphis, TN
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  • A. Pestronk MD,

    1. H. Houston Merritt Clinical Research Center for Muscular Dystrophy and Related Diseases-Department of Neurology, Washington University Medical School, Sr. Louis, MO
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  • E. Bonilla MD,

    1. H. Houston Merritt Clinical Research Center for Muscular Dystrophy and Related Diseases-Departments of Neurology, Columbia University, New york, NY
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  • Dr S. Dimauro MD

    Corresponding author
    1. H. Houston Merritt Clinical Research Center for Muscular Dystrophy and Related Diseases-Departments of Neurology, Columbia University, New york, NY
    • College of Physicians and Surgeons, Room 4-420, 630 W. 168th Street, New York, NY 10032
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Abstract

Inclusion body myositis, a chronic inflammatory disorder, is the most common cause of myopathy in adults over the age of 50. Diagnosis is based on clinical features and distinctive morphological findings by both light and electron microscopy. The causes of inclusion body myositis are still unknown. Ultrastructural mitochondrial changes and ragged- red fibers are common in patients with sporadic inclusion body myositis, and mutiple mitochondrial DNA (mtDNA) deletions have been reported in 3 such patients, suggesting that mtDNA mutations may have a pathogenetic role. We studied 56 patients with sporadic inclusion body myositis, using a combination of clinical, morphological, biochemical, and molecular genetic analyses to determine the frequency and the distribution of mtDNA deletions. Using the polymerase chain reaction, we found multiple mtDNA deletions in 73% of patients, compared to 40% of normal age-matched control subjects and 47% of disease control subjects. The presence of deletions correlated with morphological evidence of ragged-red, cytochrome c oxidase-negative fibers, and with defects of complexes I and IV of the electron transport chain. Although aging may account for a proportion of mtDNA deletions in patients with sporadic inclusion body myositis and control subjects, mtDNA alterations may be accelerated in sporadic inclusion body myositis.

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