HIGH-LEVELS OF MITOCHONDRIAL-DNA WITH AN UNSTABLE 260-BP DUPLICATION IN A PATIENT WITH MITOCHONDRIAL MYOPATHY

Other investigators reported the presence of low levels of a 260-bp he teroplasmic duplication of mitochondrial DNA in patients with mitochon drial DNA deletions and their asymptomatic mothers. In this study, we were notable to detect this polymorphism in 30 patients with mitochond rial DNA deletions, but the 260-bp duplication was detected in relativ ely high levels (32% in muscle) in a patient with a slowly progressive mitochondrial myopathy. The duplication was also present in cultured fibroblasts (10%) and in WBC (<1%). Mitochondrial dysfunction in this patient was evidenced in muscle by the presence of ragged-red fibers a nd a partial decrease in cytochrome c oxidase activity. We also detect ed low levels of mitochondrial DNA harboring a triplication of the 260 -bp region, indicating that this polymorphism is unstable. Taken toget her, our results suggest than an unstable 260-bp duplication, which in cludes important mitochondrial DNA cis-acting regulatory sequences, ma y be pathogenic per se, if present at high levels.