Mitochondrial myopathy and complex III deficiency in a patient with a new stop-codon mutation (G339X) in the cytochrome b gene.
A 19-year-old woman complained of life-long exercise intolerance and had chronic lactic acidosis. Neurological examination was normal, but muscle biopsy showed cytochrome c oxidase-positive fibers and marked complex III deficiency. Sequence analysis showed a novel stop-codon mutation (G15761A) in the mitochondrial DNA (mtDNA)-encoded cytochrome b gene, resulting in loss of the last 41 amino acids of the protein. By PCR/restriction fragment-length polymorphism (RFLP) analysis, the G15761A mutation was very abundant (73%) in the patient's muscle, barely detectable (less than 1%) in her urine, and absent in her blood; it was also absent in muscle, urine and blood from the patient's mother. This mutation fulfills all accepted criteria for pathogenicity.
Mancuso
Michelangelo
M
Department of Neurology, 4-420 Columbia University College of Physicians and Surgeons, 630 West 168th Street, New York, NY 10032, USA.
Filosto
Massimiliano
M
Stevens
J Clarke
JC
Patterson
Marc
M
Shanske
Sara
S
Krishna
Sindu
S
DiMauro
Salvatore
S
D000140:Acidosis, Lactic / Q000175:diagnosis / Q000209:etiology; D000328:Adult; D001706:Biopsy; D002908:Chronic Disease; D018389:Codon, Nonsense; D003573:Cytochrome b Group / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000235:genetics; D014450:Electron Transport Complex III / Q000172:deficiency* / Q000235:genetics; D017079:Exercise Tolerance / Q000235:genetics; D005260:Female; D006801:Humans; D017240:Mitochondrial Myopathies / Q000150:complications / Q000175:diagnosis* / Q000473:pathology; D018482:Muscle, Skeletal / Q000201:enzymology / Q000473:pathology; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D017384:Sequence Deletion
D018389:Codon, Nonsense; D003573:Cytochrome b Group; D004272:DNA, Mitochondrial; D014450:Electron Transport Complex III