MITOCHONDRIAL-DNA DEFECTS IN BRAZILIAN PATIENTS WITH CHRONIC PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA

We report herein on eleven Brazilian patients with mitochondrial DNA ( mtDNA) deletions, found among thirteen patients with chronic progressi ve external ophthalmoplegia (CPEO) and ragged-red fibers (RRF). The mo lecular data was correlated with the morphological and clinical findin gs. The muscle biopsies were studied by histochemistry, immunohistoche mistry and DNA analysis. Muscle mtDNA deletions were mapped and quanti tated by Southern blot analysis, polymerase chain reaction and sequenc ing. Of the eleven patients, ten had CPEO without multisystemic involv ement and one had Kearns-Sayre syndrome. Three patients had multiple d eletions, two of them with no apparent family history. Eight patients showed heteroplasmic single deletions, ranging in length from 2309 to 7566 bp; three of them had the same 'common deletion' of 4977 bp. The proportion of deleted mtDNA ranged from 14 to 89%. Immunohistochemical studies revealed decreased reactivity with the mtDNA-encoded subunit II of cytochrome c oxidase (COX) in all patients, but preserved activi ty with the nuclear-encoded COX subunit IV in COX-deficient fibers. Tw o cases presented a few COX-negative fibers with reduced COX IV immuno staining. We found a high frequency of mtDNA deletions in Brazilian pa tients with CPEO. There was no correlation between clinical severity, morphological findings and the size or amount of the mutated mtDNA in muscle, suggesting that there are still unknown factors influencing th e disease phenotype. (C) 1997 Elsevier Science B.V.