These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Transcription and translation of deleted mitochondrial genomes in Kearns-Sayre syndrome: implications for pathogenesis.
    Author: Nakase H, Moraes CT, Rizzuto R, Lombes A, DiMauro S, Schon EA.
    Journal: Am J Hum Genet; 1990 Mar; 46(3):418-27. PubMed ID: 1689952.
    Abstract:
    Large-scale deletions of human mitochondrial DNA (mtDNA) have been described in a clinical subgroup of mitochondrial encephalomyopathies associated with progressive external ophthalmoplegia and ragged-red fibers in skeletal muscle, including cases of Kearns-Sayre syndrome (KSS). Since the decrease in the activities of mtDNA-encoded respiratory-chain enzymes did not seem to be correlated to the sites of the deletions, the role played by the mtDNA deletions in the pathogenesis of these disorders has been unclear. To address this issue, we studied transcription and translation of deleted mtDNA in two patients with KSS harboring two different deletions. We found that the deleted genomes were transcriptionally active in both cases. Analysis of translation in one of the patients showed that the "fusion" mRNA derived from the region spanning the deletion did not seem to be translated. Thus, the biochemical defects in KSS can be explained by a lack of translation of mtDNA-encoded respiratory-chain polypeptides in some mitochondria, which, in turn, is probably due to the lack of indispensable mtDNA-encoded tRNAs in these organelles. These results imply that deleted mtDNAs may be segregated from normal genomes in this group of diseases. It seems likely that the absence of translation in proliferating mitochondria containing partially deleted genomes plays a major role in the pathogenesis of these disorders.
    [Abstract] [Full Text] [Related] [New Search]