MULTIPLE MITOCHONDRIAL-DNA DELETIONS IN SPORADIC INCLUSION-BODY MYOSITIS - A STUDY OF 56 PATIENTS

Inclusion body myositis, a chronic inflammatory disorder, is the most common cause of myopathy in adults over the age of 50. Diagnosis is ba sed on clinical features and distinctive morphological findings by bot h light and electron microscopy. The causes of inclusion body myositis are still unknown. Ultrastructural mitochondrial changes and ragged-r ed fibers are common in patients with sporadic inclusion body myositis , and mutiple mitochondrial DNA (mtDNA) deletions have been reported i n 3 such patients, suggesting that mtDNA mutations may have a pathogen etic role. We studied 56 patients with sporadic inclusion body myositi s, using a combination of clinical, morphological, biochemical, and mo lecular genetic analyses to determine the frequency and the distributi on of mtDNA deletions. Using the polymerase chain reaction, we found m ultiple 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 comple xes I and TV of the electron transport chain. Although aging may accou nt for a proportion of mtDNA deletions in patients with sporadic inclu sion body myositis and control subjects, mtDNA alterations may be acce lerated in sporadic inclusion body myositis.