title: A mitochondrial DNA variant, identified in Leber hereditary optic neuropathy patients, which extends the amino acid sequence of cytochrome c oxidase subunit I.
abstract: A G-to-A transition at nucleotide pair (np) 7444 in the mtDNA was found to correlate with Leber hereditary optic neuropathy (LHON). The mutation eliminates the termination codon of the cytochrome c oxidase subunit I (COI) gene, extending the COI polypeptide by three amino acids. The mutation was discovered as an XbaI restriction-endonuclease-site loss present in 2 (9.1%) of 22 LHON patients who lacked the np 11778 LHON mutation and in 6 (1.1%) of 545 unaffected controls. The mutant polypeptide has an altered mobility on SDS-PAGE, suggesting a structural alteration, and the cytochrome c oxidase enzyme activity of patient lymphocytes is reduced approximately 40% relative to that in controls. These data suggest that the np 7444 mutation results in partial respiratory deficiency and thus contributes to the onset of LHON.
authors.affiliation: Department of Genetics and Molecular Medicine, Emory University School of Medicine, Atlanta, GA 30322.
authors.forename: M D
authors.initials: MD
authors.lastname: Brown
authors.forename: C C
authors.initials: CC
authors.lastname: Yang
authors.forename: I
authors.initials: I
authors.lastname: Trounce
authors.forename: A
authors.initials: A
authors.lastname: Torroni
authors.forename: M T
authors.initials: MT
authors.lastname: Lott
authors.forename: D C
authors.initials: DC
authors.lastname: Wallace
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D004272:DNA, Mitochondrial / Q000235:genetics*; D003576:Electron Transport Complex IV / Q000235:genetics* / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D015418:Optic Atrophies, Hereditary / Q000201:enzymology / Q000235:genetics*; D010802:Phylogeny; D013728:Terminator Regions, Genetic
chemical_list: D004272:DNA, Mitochondrial; D003576:Electron Transport Complex IV