title: Two novel pathogenic mitochondrial DNA mutations affecting organelle number and protein synthesis. Is the tRNA(Leu(UUR)) gene an etiologic hot spot?
abstract: We identified two patients with pathogenic single nucleotide changes in two different mitochondrial tRNA genes: the first mutation in the tRNA(Asn) gene, and the ninth known mutation in the tRNA(Leu(UUR)) gene. The mutation in tRNA(Asn) was associated with isolated ophthalmoplegia, whereas the mutation in tRNA(Leu(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 tRNA(Leu(UUR)) gene suggests that this region is an "etiologic hot spot" in mitochondrial disease.
authors.affiliation: Department of Genetics & Development, College of Physicians & Surgeons, Columbia University, New York 10032.
authors.forename: C T
authors.initials: CT
authors.lastname: Moraes
authors.forename: F
authors.initials: F
authors.lastname: Ciacci
authors.forename: E
authors.initials: E
authors.lastname: Bonilla
authors.forename: C
authors.initials: C
authors.lastname: Jansen
authors.forename: M
authors.initials: M
authors.lastname: Hirano
authors.forename: N
authors.initials: N
authors.lastname: Rao
authors.forename: R E
authors.initials: RE
authors.lastname: Lovelace
authors.forename: L P
authors.initials: LP
authors.lastname: Rowland
authors.forename: E A
authors.initials: EA
authors.lastname: Schon
authors.forename: S
authors.initials: S
authors.lastname: DiMauro
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003062:Codon / Q000235:genetics; D004272:DNA, Mitochondrial / Q000235:genetics*; D004679:Encephalomyelitis / Q000235:genetics*; D004798:Enzymes / Q000235:genetics; D005260:Female; D005796:Genes; D006801:Humans; D017243:MERRF Syndrome / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000378:metabolism* / Q000473:pathology*; D017240:Mitochondrial Myopathies / Q000235:genetics* / Q000473:pathology; D008969:Molecular Sequence Data; D009132:Muscles / Q000473:pathology; D009690:Nucleic Acid Conformation; D017354:Point Mutation; D012348:RNA, Transfer, Asn / Q000235:genetics*; D012356:RNA, Transfer, Leu / Q000235:genetics*; D017384:Sequence Deletion; D012689:Sequence Homology, Nucleic Acid
chemical_list: D003062:Codon; D004272:DNA, Mitochondrial; D004798:Enzymes; D012348:RNA, Transfer, Asn; D012356:RNA, Transfer, Leu