Author(s): R. W. Taylor;P. F. Chinnery;M. J. Bates;M. J. Jackson;M. A. Johnson;R. M. Andrews;D. M. Turnbull
Abstract: We report a new mutation, a G to A transition at nucleotide position 4298 within the mitochondrial tRNA(Ile) gene in a patient with chronic progressive external ophthalmoplegia and multiple sclerosis. The mutation, which alters an evolutionary conserved nucleotide within the anticodon stem, was heteroplasmic in skeletal muscle but was not present in the patient's blood. Single fibre PCR analysis revealed significantly higher levels of the G4298A mutation in cytochrome c oxidase (COX) negative fibres than in COX-positive fibres. This mutation represents the seventh pathogenic nucleotide substitution to be found in this gene and as such confirms the tRNA(Ile) gene as a susceptible "hot spot" for mitochondrial DNA point mutations. Of particular interest is that this patient has the clinical features of both multiple sclerosis and a mitochondrial DNA disorder.
Notes: 0006-291x Case Reports Journal Article
Keywords: Animals Base Sequence Comparative Study DNA, Mitochondrial/chemistry/*genetics Electron Transport Complex IV/metabolism Female Humans Middle Aged Mitochondrial Myopathies/complications/genetics/metabolism Molecular Sequence Data Multiple Sclerosis/*complications/*genetics/metabolism Muscle Fibers/metabolism Muscle, Skeletal/metabolism Nucleic Acid Conformation Ophthalmoplegia, Chronic Progressive External/*complications/*genetics/metabolism *Point Mutation RNA, Transfer, Ile/*genetics Research Support, Non-U.S. Gov't Sequence Homology, Nucleic Acid Species Specificity
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Professor Patrick Chinnery
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