ARE DUPLICATIONS OF MITOCHONDRIAL-DNA CHARACTERISTIC OF KEARNS-SAYRE SYNDROME

The phenotypes of Kearns - Sayre syndrome (KSS) and chronic progressiv e external ophthalmoplegia (CPEO) are closely associated with deletion s of mitochondrial DNA (mtDNA). Recent evidence suggesting that more t han one type of rearrangement may be present in KSS led us to reinvest igate 18 patients with KSS or CPEO for the presence of mtDNA rearrange ments other than deletion. mtDNA duplication was detectable in 10 of 1 0 patients with KSS, while deletion monomers were the only recombinant mtDNA easily detectable in eight of eight patients with CPEO. Deletio n dimers were found only in cases having duplications. Thus, duplicati ons of mtDNA seem to be a hallmark of KSS, including a patient where P earson's syndrome was the first manifestation. We suggest that duplica tion of mtDNA is characteristic of the early-onset disease KSS, and th at the balance of mtDNA rearrangements may be central to the pathogene sis of this unique group of disorders.