A novel nonsense mutation (Q352X) in the mitochondrial cytochrome b gene associated with a combined deficiency of complexes I and III.

We identified a novel mitochondrial cytochrome b mutation in a patient with progressive exercise intolerance, muscle cramps and lactic acidosis. A marked reduction of the enzymatic activities of respiratory chain complexes I and III was found in muscle biopsy. The mutation was a heteroplasmic C15800T transition, determining a stop-codon at amino acid position 352 (Q352X). Mutant mtDNA was approximately 45% of total genomes in muscle, while it was absent in all of the other examined tissues of the patient and in lymphocytes of the patient's mother. Clinical presentation and laboratory findings strongly support the hypothesis that this mutation is the primary cause of the disease in our patient.