Abstract
We sequenced all mitochondrial tRNA genes in a 61-year-old man with chronic progressive external ophthalmoplegia and mitochondrial myopathy but without mtDNA rearrangements, and identified a heteroplasmic m.3244G>A mutation in the tRNA(Leu(UUR)) gene. This mutation had been previously associated with the MELAS phenotype, but not described in any detail. The mutation load in muscle was 84% and COX-negative fibers harbored greater levels of mutant genomes than COX-positive fibers. The m.3244G>A mutation affects a highly conserved nucleotide in the dihydrouridine loop and has been associated with a wobble modification deficiency of the mutant tRNA.
Publication types
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Case Reports
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Base Sequence
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Conserved Sequence / genetics
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DNA Mutational Analysis
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DNA, Mitochondrial / genetics*
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Disease Progression
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Genetic Predisposition to Disease / genetics*
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Humans
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Male
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Middle Aged
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Mitochondrial Diseases / genetics*
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Mitochondrial Diseases / metabolism
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Mitochondrial Diseases / physiopathology
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Muscle Fibers, Skeletal / metabolism
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Muscle Fibers, Skeletal / pathology
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Mutation / genetics*
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Nucleotides / genetics
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Oculomotor Muscles / metabolism
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Oculomotor Muscles / physiopathology
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Ophthalmoplegia, Chronic Progressive External / genetics*
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Ophthalmoplegia, Chronic Progressive External / metabolism
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Ophthalmoplegia, Chronic Progressive External / physiopathology
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Quadriceps Muscle / metabolism
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Quadriceps Muscle / pathology
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RNA, Transfer, Leu / genetics*
Substances
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DNA, Mitochondrial
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Nucleotides
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RNA, Transfer, Leu