CORRELATION BETWEEN THE CLINICAL SYMPTOMS AND THE PROPORTION OF MITOCHONDRIAL-DNA CARRYING THE 8993-POINT MUTATION IN THE NARP SYNDROME

We describe a four-generation family with a maternally inherited mitoc hondrial disorder. The symptoms were restricted to the CNS and muscle, the most common features being subacute necrotizing encephalomyopathy , cognitive impairment, ataxia, retinitis pigmentosa, infantile spasms , and optic atrophy. A point mutation at the nucleotide 8993 of the ge ne encoding subunit 6 of the ATP synthase, associated with the neuroge nic muscle weakness, ataxia, retinitis pigmentosa (NARP) syndrome, was shown to be inherited maternally in this family, and a clear correlat ion was found between the clinical severity of the disease and the pro portion of mutant mtDNA. Analysis of oxidative phosphorylation in mito chondria carrying 80% mutant mitochondrial DNA showed a reduction of t he ATP generation rate coupled to substrate oxidation.