Multiple mitochondrial DNA deletions in sporadic inclusion body myositis: a study of 56 patients
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F M Santorelli1, M Sciacco, K Tanji
1H. Houston Merritt Clinical Research Center for Muscular Dystrophy and Related Diseases--Department of Neurology, Columbia University, New York, NY, USA.
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 multiple [correction of 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.
Insights
Mitochondrial DNA deletions are common in inclusion body myositis, a muscle disorder affecting older adults. These genetic alterations may accelerate disease progression, suggesting a role in sporadic inclusion body myositis pathogenesis.
Area of Science:
- Neurology
- Genetics
- Mitochondrial Biology
Background:
- Inclusion body myositis (IBM) is the most frequent myopathy in adults over 50.
- Diagnosis relies on clinical presentation and microscopy.
- The etiology of IBM remains unclear, though mitochondrial DNA (mtDNA) deletions are suspected.
Purpose of the Study:
- To investigate the frequency and distribution of mtDNA deletions in sporadic IBM.
- To correlate mtDNA deletions with clinical and morphological findings.
Main Methods:
- Studied 56 sporadic IBM patients using clinical, morphological, biochemical, and molecular genetic analyses.
- Employed polymerase chain reaction (PCR) to detect mtDNA deletions.
- Examined ragged-red fibers and cytochrome c oxidase activity.
Main Results:
- Multiple mtDNA deletions found in 73% of IBM patients, versus 40% in controls.
- Deletions correlated with ragged-red fibers and defects in electron transport chain complexes I and IV.
- mtDNA alterations may be accelerated in IBM, beyond age-related changes.
Conclusions:
- Multiple mtDNA deletions are frequent in sporadic IBM.
- These deletions are associated with specific pathological features and biochemical defects.
- Accelerated mtDNA alterations may contribute to IBM pathogenesis.