title: Early-onset multisystem mitochondrial disorder caused by a nonsense mutation in the mitochondrial DNA cytochrome C oxidase II gene.
abstract: We report the first nonsense mutation (G7896A) in the mtDNA gene for subunit II of cytochrome c oxidase (COX) in a patient with early-onset multisystem disease and COX deficiency in muscle. The mutation was heteroplasmic in muscle, blood, and fibroblasts from the patient and abundantly present in COX-deficient fibers, but less abundant in COX-positive fibers; it was not found in blood samples from the patient's asymptomatic maternal relatives. Immunoblot analysis showed a reduced concentration of both COX II and COX I polypeptides, suggesting impaired assembly of COX holoenzyme.
authors.affiliation: Centro de Investigación and Departamento de Neuropatología, Hospital Universitario, Madrid, Spain.
authors.forename: Y
authors.initials: Y
authors.lastname: Campos
authors.forename: A
authors.initials: A
authors.lastname: García-Redondo
authors.forename: M A
authors.initials: MA
authors.lastname: Fernández-Moreno
authors.forename: M
authors.initials: M
authors.lastname: Martínez-Pardo
authors.forename: G
authors.initials: G
authors.lastname: Goda
authors.forename: J C
authors.initials: JC
authors.lastname: Rubio
authors.forename: M A
authors.initials: MA
authors.lastname: Martín
authors.forename: P
authors.initials: P
authors.lastname: del Hoyo
authors.forename: A
authors.initials: A
authors.lastname: Cabello
authors.forename: B
authors.initials: B
authors.lastname: Bornstein
authors.forename: R
authors.initials: R
authors.lastname: Garesse
authors.forename: J
authors.initials: J
authors.lastname: Arenas
mesh_terms: D002675:Child, Preschool; D018389:Codon, Nonsense / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000096:biosynthesis / Q000235:genetics*; D003576:Electron Transport Complex IV / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D017240:Mitochondrial Myopathies / Q000201:enzymology / Q000235:genetics*; D018482:Muscle, Skeletal / Q000201:enzymology; D010641:Phenotype; D012150:Polymorphism, Restriction Fragment Length
chemical_list: D018389:Codon, Nonsense; D004272:DNA, Mitochondrial; C117108:cytochrome C oxidase subunit II; D003576:Electron Transport Complex IV