Classical mitochondrial phenotypes without mtDNA mutations: the possible role of nuclear genes

The authors analyzed the total mitochondrial (mt) genome in 15 patients with classic mitochondrial phenotypes. Novel somatic mtDNA mutations in two patients with chronic progressive external ophthalmoplegia were identified. Total automated mtDNA genome analysis did not reveal other pathogenic mtDNA mutations. The authors conclude that classic mitochondrial phenotypes, including those with adult onset, may occur in the absence of mtDNA mutations. Nuclear gene mutations may be the cause.