A mitochondrial DNA variant, identified in Leber hereditary optic neuropathy patients, which extends the amino acid sequence of cytochrome c oxidase subunit I.
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.
Brown
M D
MD
Department of Genetics and Molecular Medicine, Emory University School of Medicine, Atlanta, GA 30322.
Yang
C C
CC
Trounce
I
I
Torroni
A
A
Lott
M T
MT
Wallace
D C
DC
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
D004272:DNA, Mitochondrial; D003576:Electron Transport Complex IV