Mitochondrial DNA-related diseases associated with single large-scale deletions and point mutations

Abstract Mitochondria are fundamental to cellular metabolism and provide the major source of energy in human cells. Mutations in nuclear- and mitochondrial DNA (mtDNA)-encoded genes cause a variety of incurable mitochondrial disorders. The prevalence of mtDNA mutations in an adult population is estimated to be 1 in 5000, ranking mtDNA diseases among the most commonly inherited neuromuscular disorders. MtDNA mutations account for a significant proportion of mitochondrial diseases, particularly in adults, and more than 250 different potentially pathogenic variants of mtDNA are reported. This chapter discusses single large-scale mtDNA deletions and the confirmed pathogenic mtDNA point mutations and their clinical manifestations, and the remarkable complexity of mtDNA-related mutation genetics, despite the molecule’s small size. We also describe the continuously evolving diagnostic approach to mtDNA mutation diseases, and summarize existing and emerging treatment options for this group of disorders.