Early-onset multisystem mitochondrial disorder caused by a nonsense mutation in the mitochondrial DNA cytochrome C oxidase II gene.
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.
Campos
Y
Y
Centro de Investigación and Departamento de Neuropatología, Hospital Universitario, Madrid, Spain.
García-Redondo
A
A
Fernández-Moreno
M A
MA
Martínez-Pardo
M
M
Goda
G
G
Rubio
J C
JC
Martín
M A
MA
del Hoyo
P
P
Cabello
A
A
Bornstein
B
B
Garesse
R
R
Arenas
J
J
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
D018389:Codon, Nonsense; D004272:DNA, Mitochondrial; C117108:cytochrome C oxidase subunit II; D003576:Electron Transport Complex IV