A new mtDNA mutation associated with a progressive encephalopathy and cytochrome c oxidase deficiency

The authors describe a novel pathogenic G5540A transition in the mitochondr ial transfer RNA (tRNA)(Trp) gene of a sporadic encephalomyopathy character ized by spinocerebellar ataxia. Clinical features also included neurosensor ial deafness, peripheral neuropathy, and dementia. Biochemistry revealed a severe reduction of cytochrome c oxidase (COX) activity. Single-fiber PCR d emonstrated higher levels of mutant genomes in COX-negative ragged red fibe rs than in normal fibers. These findings confirm that COX is more susceptib le than other respiratory chain complexes to mutations in the mitochondrial tRNA(Trp) gene.