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

Large-scale deletions and point mutations of the mitochondrial DNA are gene rally accepted as being involved in the pathogenesis of diseases associated with mitochondrial encephalomyopathies such as Kearns-Sayre syndrome and c hronic progressive external ophthalmoplegia (CPEO). We screened suspected p atients 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 familiar occurrence of a tRNA(Leu(UUR)) T3250C point mut ation in a young female patient clinically diagnosed with CPEO. This deleti on is not flanked by direct repeats, so slip replication and homologous rec ombination do not seem likely as the mechanism of origin. Here, we point ou t the possible role of a single base replacement as a promoter of a deleter ious event when exceeding an organ-specific threshold of heteroplasmy. Dist urbances of energy metabolism by means of accumulation of reactive oxygen s pecies, thus, may severely interfere in the ATP production of the respirato ry chain. (C) 1999 Wiley-Liss, Inc.