Chronic progressive external ophthalmoplegia with a novel mitochondrial DNA deletion and a mutation in the tRNALEU(UUR) gene

Large‐scale deletions and point mutations of the mitochondrial DNA are generally accepted as being involved in the pathogenesis of diseases associated with mitochondrial encephalomyopathies such as Kearns‐Sayre syndrome and chronic progressive external ophthalmoplegia (CPEO). We screened suspected patients using polymerase chain reaction techniques, Southern blot analyses, and muscle biopsy specimens. We report on a novel 4,953‐base pair deletion associated with a familial occurrence of a tRNA^Leu(UUR) T3250C point mutation in a young female patient clinically diagnosed with CPEO. This deletion is not flanked by direct repeats, so slip replication and homologous recombination do not seem likely as the mechanism of origin. Here, we point out the possible role of a single base replacement as a promoter of a deleterious event when exceeding an organ‐specific threshold of heteroplasmy. Disturbances of energy metabolism by means of accumulation of reactive oxygen species, thus, may severely interfere in the ATP production of the respiratory chain. Drug Dev. Res. 46:80–85, 1999. © 1999 Wiley‐Liss, Inc.