title: A novel heteroplasmic tRNA(Leu(CUN)) mtDNA point mutation associated with chronic progressive external ophthalmoplegia.
abstract: We have sequenced all mitochondrial tRNA genes from a patient with chronic progressive external ophthalmoplegia (CPEO) and mitochondrial myopathy, who had no detectable large mtDNA deletions. Direct sequencing failed to detect previously reported mutations and showed a heteroplasmic mutation at nucleotide 12,276 in the tRNA(Leu(CUN)) gene, in the dihydrouridine stem, which is highly conserved through the species during evolution. RFLP analyses confirmed that 18% of muscle mtDNA harbored the mutation, while it was absent from DNA of fibroblasts and lymphocytes of the proband and in 110 patients with other encephalomyopathies. To date, besides large and single nucleotide deletions, several point mutations on mitochondrial tRNA genes have been reported in CPEO patients, but only three were in the gene coding for tRNA(Leu(CUN)).
authors.affiliation: Department of Neurological and Behavioural Sciences, University of Siena, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Cardaioli
authors.forename: Paola
authors.initials: P
authors.lastname: Da Pozzo
authors.forename: Elena
authors.initials: E
authors.lastname: Radi
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Dotti
authors.forename: Antonio
authors.initials: A
authors.lastname: Federico
mesh_terms: D000818:Animals; D001483:Base Sequence; D004272:DNA, Mitochondrial / Q000235:genetics*; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism; D017240:Mitochondrial Myopathies / Q000235:genetics*; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D017246:Ophthalmoplegia, Chronic Progressive External / Q000235:genetics*; D017354:Point Mutation; D012150:Polymorphism, Restriction Fragment Length; D012356:RNA, Transfer, Leu / Q000235:genetics*; D014529:Uridine / Q000031:analogs & derivatives* / Q000737:chemistry
chemical_list: D004272:DNA, Mitochondrial; D012356:RNA, Transfer, Leu; C010922:5,6-dihydrouridine; D014529:Uridine