Exercise intolerance resulting from a muscle-restricted mutation in the mitochondrial tRNA(Leu (CUN)) gene

BACKGROUND. Some patients presenting with isolated lifelong exercise intole rance and ragged-red fibres, harbour skeletal-muscle restricted mutations i n their mitochondrial DNA. AIM. To identify the molecular defect in a patient presenting with lifelong exercise intolerance, ragged-red fibres and deficiencies of complexes III and IV in skeletal muscle. METHODS. The muscle biopsy was studied for activities of the respiratory ch ain, histochemical stains, and sequencing the tRNA genes of mitochondrial D NA. RESULTS. The patient had a heteroplasmic mutation in the tRNA(Leu(CUN)) gen e of mitochondrial DNA (G12334A). Clinical and morphological data as well a s restriction fragment length polymorphism (RFLP) and single-fibre polymera se chain reaction (PCR) analyses strongly indicate that this molecular defe ct is the primary cause of the myopathy. CONCLUSION. Mutations in any mitochondrial gene should be considered in the differential diagnosis of patients with lifelong exercise intolerance, eve n when the neurological examination is normal.