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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 multiple 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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autoimmune disease
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inclusion bodies
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inclusion body myositis
mitochondrial disease
muscle biopsy
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myopathy,inclusion body,hereditary
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