title: A microdeletion in cytochrome c oxidase (COX) subunit III associated with COX deficiency and recurrent myoglobinuria.
abstract: We have identified a 15-bp microdeletion in a highly conserved region of the mitochondrially encoded gene for cytochrome c oxidase (COX) subunit III in a patient with severe isolated COX deficiency and recurrent myoglobinuria. The mutant mitochondrial DNA (mtDNA) comprised 92% of the mtDNA in muscle and 0.7% in leukocytes. Immunoblots and immunocytochemistry suggested a lack of assembly or instability of the complex. Microdissected muscle fibres revealed significantly higher portions of mutant mtDNA in COX-negative than in COX-positive fibres. This represents the first case of isolated COX deficiency to be defined at the molecular level.
authors.affiliation: Department of Molecular and Medical Genetics, Oregon Health Sciences University, Portland 97201-3098, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Keightley
authors.forename: K C
authors.initials: KC
authors.lastname: Hoffbuhr
authors.forename: M D
authors.initials: MD
authors.lastname: Burton
authors.forename: V M
authors.initials: VM
authors.lastname: Salas
authors.forename: W S
authors.initials: WS
authors.lastname: Johnston
authors.forename: A M
authors.initials: AM
authors.lastname: Penn
authors.forename: N R
authors.initials: NR
authors.lastname: Buist
authors.forename: N G
authors.initials: NG
authors.lastname: Kennaway
mesh_terms: D000293:Adolescent; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D030401:Cytochrome-c Oxidase Deficiency; D004247:DNA / Q000235:genetics; D004272:DNA, Mitochondrial / Q000235:genetics; D003576:Electron Transport Complex IV / Q000737:chemistry / Q000235:genetics*; D005260:Female; D005838:Genotype; D006651:Histocytochemistry; D006801:Humans; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000201:enzymology; D009212:Myoglobinuria / Q000201:enzymology* / Q000235:genetics*; D010641:Phenotype; D011487:Protein Conformation; D012008:Recurrence; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid
chemical_list: D004272:DNA, Mitochondrial; D004247:DNA; D003576:Electron Transport Complex IV