The mitochondrial tRNA(Leu(UUR)) mutation in mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes (MELAS): Genetic, biochemical, and morphological correlations in skeletal muscle

C. T. Moraes, E. Ricci, E. Bonilla, S. DiMauro, E. A. Schon

Research output: Contribution to journalArticle

239 Scopus citations

Abstract

Mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes (MELAS) has recently been associated with an A→G transition at position 3243 within the mitochondrial tRNALeu(UUR) gene. Besides altering the tRNALeu(UUR) sequence, this point mutation lies within a DNA segment responsible for transcription termination of the rRNA genes. We have studied the distribution and expression of mutant mtDNAs in muscle biopsies from MELAS patients. Histochemical, immunohistochemical, and single-fiber PCR analysis showed that ragged-red fibers (RRF) are associated both with high levels of mutant mitochondrial genomes (>85% mutant mtDNA) and with a partial cytochrome c oxidase deficiency. By quantitative in situ hybridization, the steady-state ratios of mRNAs:rRNAs were found to be similar to controls in six of eight patients studied. In two other patients the relative levels of heavy-strand mRNAs were slightly increased, but a patient with myoclonic epilepsy and RRF also exhibited a similar increase. These results directly correlate the A→G transition at mtDNA position 3243 with muscle mitochondrial proliferation, partial respiratory-chain impairment, decreased mitochondrially synthesized protein content, and no specific alterations in mitochondrial ratios of mRNAs:rRNAs.

Original languageEnglish (US)
Pages (from-to)934-949
Number of pages16
JournalAmerican journal of human genetics
Volume50
Issue number5
StatePublished - Jun 1 1992
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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