Two novel pathogenic mitochondrial DNA mutations affecting organelle number and protein synthesis: Is the tRNALeu(UUR) gene an etiologic hot spot?

Carlos T Moraes, Federica Ciacci, Eduarde Bonilla, Christopher Jansen, Michio Hirano, Nagbhushan Rao, Robert E. Lovelace, Lewis P. Rowland, Eric A. Schon, Salvatore DiMauro

Research output: Contribution to journalArticle

198 Citations (Scopus)

Abstract

We identified two patients with pathogenic single nucleotide changes in two different mitochondrial tRNA genes: the first mutation in the tRNAAsn gene, and the ninth known mutation in the tRNALeu(UUR) gene. The mutation in tRNAAsn was associated with isolated ophthalmoplegia, whereas the mutation in tRNALeu(UUR) caused a neurological syndrome resembling MERRF (myoclonus epilepsy and ragged-red fibers) plus optic neuropathy, retinopathy, and diabetes. Both mutations were heteroplasmic, with higher percentages of mutant mtDNA in affected tissues, and undetectable levels in maternal relatives. Analysis of single muscle fibers indicated that morphological and biochemical alterations appeared only when the proportions of mutant mtDNA exceeded 90% of the total cellular mtDNA pool. The high incidence of mutations in the tRNALeu(UUR) gene suggests that this region is an "etiologic hot spot" in mitochondrial disease.

Original languageEnglish
Pages (from-to)2906-2915
Number of pages10
JournalJournal of Clinical Investigation
Volume92
Issue number6
StatePublished - Dec 1 1993

Fingerprint

RNA, Transfer, Leu
Mitochondrial DNA
Organelles
Mutation
RNA, Transfer, Asn
Genes
Proteins
Myoclonic Epilepsy
Ophthalmoplegia
Mitochondrial Diseases
Optic Nerve Diseases
Mitochondrial Genes
Transfer RNA
Nucleotides
Mothers
Muscles
Incidence

Keywords

  • Diabetes
  • Mitochondrial disorders
  • Mitochondrial DNA
  • Ophthalmoparesis
  • tRNA identity

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Two novel pathogenic mitochondrial DNA mutations affecting organelle number and protein synthesis : Is the tRNALeu(UUR) gene an etiologic hot spot? / Moraes, Carlos T; Ciacci, Federica; Bonilla, Eduarde; Jansen, Christopher; Hirano, Michio; Rao, Nagbhushan; Lovelace, Robert E.; Rowland, Lewis P.; Schon, Eric A.; DiMauro, Salvatore.

In: Journal of Clinical Investigation, Vol. 92, No. 6, 01.12.1993, p. 2906-2915.

Research output: Contribution to journalArticle

Moraes, CT, Ciacci, F, Bonilla, E, Jansen, C, Hirano, M, Rao, N, Lovelace, RE, Rowland, LP, Schon, EA & DiMauro, S 1993, 'Two novel pathogenic mitochondrial DNA mutations affecting organelle number and protein synthesis: Is the tRNALeu(UUR) gene an etiologic hot spot?', Journal of Clinical Investigation, vol. 92, no. 6, pp. 2906-2915.
Moraes, Carlos T ; Ciacci, Federica ; Bonilla, Eduarde ; Jansen, Christopher ; Hirano, Michio ; Rao, Nagbhushan ; Lovelace, Robert E. ; Rowland, Lewis P. ; Schon, Eric A. ; DiMauro, Salvatore. / Two novel pathogenic mitochondrial DNA mutations affecting organelle number and protein synthesis : Is the tRNALeu(UUR) gene an etiologic hot spot?. In: Journal of Clinical Investigation. 1993 ; Vol. 92, No. 6. pp. 2906-2915.
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