The mitochondrial DNA A3243G mutation in Portugal: clinical and molecular studies in 5 families

Out of 90 Portuguese patients with mitochondrial cytopathy, six harbored th e A3243G mutation in the mtDNA tRNA(Leu(UUR)) gene ('MELAS mutation'). They had heterogeneous clinical features, including myopathy with stroke-like e pisodes, progressive external ophthalmoparesis, diabetes mellitus, and suba cute encephalopathy. Histochemical and biochemical analyses of muscle biops ies showed abundant ragged-red fibers reacting positively with the cytochro me oxidase stain, and decreased respiratory chain enzyme activities. On ave rage, the proportion of mutated mtDNA was 67% (20-88%) in tissues from pati ents and 21% (0-49%) in blood from 20 maternal relatives. The proportion of mutated mitochondrial genomes in muscle did not correlate with clinical pr esentation or duration of disease. This study, the first in Portuguese pati ents, confirms the frequent occurrence of the A3243G mutation in patients w ith mitochondrial diseases, and emphasises the usefulness of genetic testin g in reaching a correct diagnosis. (C) 1999 Elsevier Science BN. All rights reserved.