ABSTRACT
This chapter describes the recent advances in understanding of mitochondrial genetics that are directly relevant to understanding of disease that is directly due to defects of the mitochondrial genome. The stringent criteria depend upon a good knowledge of polymorphic sites in the background population. Other mitochondrial DNA (mtDNA) rearrangements may cause disease, and a mtDNA inversion was described in a patient with a myopathy and myoglobinuria. Despite these complexities, when it has been possible to accumulate sufficient data to study the relationship between mutation load and clinical phenotype, it appears that, at least for some mutations, the proportion of mutant mtDNA is the overriding factor in determining clinical phenotype. Some patients with mtDNA disease have an instantly recognizable clinical phenotype, such as Leber’s hereditary optic neuropathy. Differences in heteroplasmy and tissue vulnerability can only be part of the explanation, and additional genetic and environmental factors are probably also important.
