MERRF patients, mtDNA mutation

It is well established that mitochondrial function defects are not severe until the proportion of mutant mtDNA reaches a high level, which forms the basis of the concept of the threshold effect. In skeletal muscle, the level of the A3243G mutation is related to the severity of strokelike episodes, epilepsy, and dementia in patients with MELAS syndrome (C6, H14, PI). Similarly, the level of the A8344G mutation is correlated with the degree of cerebellar ataxia and myoclonus in patients with MERRF syndrome (C6). Thus, molecular genetic analysis of mtDNA mutations in muscle biopsies usually provides more definitive diagnosis of... 

On the other hand, defective respiratory function elicited by the mtDNA mutation contributes to an increase in the production of ROS and free radicals, thereby causing higher oxidative stress and severe oxidative damage in affected cells (P2, W6). Because either enhanced oxidative stress or disruption of calcium homeostasis is an important factor in the triggering of cell death, mitochondrial dysfunction in tissue cells from MELAS and MERRF patients may contribute significantly to the pathogenesis of these diseases. 

A number of distinctive syndromes have been shown to be associated with specific point mutations of mtDNA (Table 1) (M15, S4, S14). Several point mutations have been reported to occur at tRNA genes in the mitochondrial genome. For example, the A8344G mutation is present in patients with MERRF syndrome (S9), whereas the A3243G mutation of mtDNA was first identified in a subgroup of patients with MELAS syndrome (G4). MERRF syndrome was the first... 

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