Joanna Poulton, Karl J. Morten, Katharina Weber, Garry K. Brown, Laurence Bindoff; Are duplications of mitochondrial DNA characteristic of Kearns—Sayre syndrome?. Hum Mol Genet 1994; 3 (6): 947-951. doi: 10.1093/hmg/3.6.947
The phenotypes of Kearns–Sayre syndrome (KSS) and chronic progressive external ophthalmoplegia (CPEO) are closely associated with deletions of mitochondrial DNA (mtDNA). Recent evidence suggesting that more than one type of rearrangement may be present in KSS led us to reinvestigate 18 patients with KSS or CPEO for the presence of mtDNA rearrangements other than deletion. mtDNA duplication was detectable in 10 of 10 patients with KSS, while deletion monomers were the only recombinant mtDNA easily detectable in eight of eight patients with CPEO. Deletion dimers were found only in cases having duplications. Thus, duplications of mtDNA seem to be a hallmark of KSS, including a patient where Pearson's syndrome was the first manifestation. We suggest that duplication of mtDNA is characteristic of the early-onset disease KSS, and that the balance of mtDNA rearrangements may be central to the pathogenesis of this unique group of disorders.