title: An mtDNA mutation in the initiation codon of the cytochrome C oxidase subunit II gene results in lower levels of the protein and a mitochondrial encephalomyopathy.
abstract: A novel heteroplasmic 7587T-->C mutation in the mitochondrial genome which changes the initiation codon of the gene encoding cytochrome c oxidase subunit II (COX II), was found in a family with mitochondrial disease. This T-->C transition is predicted to change the initiating methionine to threonine. The mutation load was present at 67% in muscle from the index case and at 91% in muscle from the patient's clinically affected son. Muscle biopsy samples revealed isolated COX deficiency and mitochondrial proliferation. Single-muscle-fiber analysis revealed that the 7587C copy was at much higher load in COX-negative fibers than in COX-positive fibers. After microphotometric enzyme analysis, the mutation was shown to cause a decrease in COX activity when the mutant load was >55%-65%. In fibroblasts from one family member, which contained >95% mutated mtDNA, there was no detectable synthesis or any steady-state level of COX II. This new mutation constitutes a new mechanism by which mtDNA mutations can cause disease-defective initiation of translation.
authors: Departments of Neurology, The Medical School, University of Newcastle upon Tyne, Newcastle upon Tyne, United Kingdom NE2 4HH.
authors: K M
authors: KM
authors: Clark
authors: R W
authors: RW
authors: Taylor
authors: M A
authors: MA
authors: Johnson
authors: P F
authors: PF
authors: Chinnery
authors: Z M
authors: ZM
authors: Chrzanowska-Lightowlers
authors: R M
authors: RM
authors: Andrews
authors: I P
authors: IP
authors: Nelson
authors: N W
authors: NW
authors: Wood
authors: P J
authors: PJ
authors: Lamont
authors: M G
authors: MG
authors: Hanna
authors: R N
authors: RN
authors: Lightowlers
authors: D M
authors: DM
authors: Turnbull
mesh_terms: D000328:Adult; D018387:Codon, Initiator / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000235:genetics*; D003576:Electron Transport Complex IV / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017237:Mitochondrial Encephalomyopathies / Q000201:enzymology / Q000235:genetics*; D017354:Point Mutation / Q000235:genetics*; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000032:analysis; D012349:RNA, Transfer, Asp / Q000235:genetics; D012362:RNA, Transfer, Ser / Q000235:genetics
chemical_list: D018387:Codon, Initiator; D004272:DNA, Mitochondrial; D012333:RNA, Messenger; D012349:RNA, Transfer, Asp; D012362:RNA, Transfer, Ser; C117108:cytochrome C oxidase subunit II; D003576:Electron Transport Complex IV