This chapter presents an overview of the major diseases that result from mitochondrial DNA (mtDNA) mutations. The mutations are divided into two types: mutations that affect mitochondrial protein-encoding genes and those that affect mitochondrial protein synthesis. Diseases that result from mutations in mitochondrial protein-encoding genes include Leber's hereditary optic neuropathy (LHON) and neuropathy, ataxia, and retinitis pigmentosa (NARP). The diseases that result from mutations in mitochondrial protein synthesis genes include Kearns-Sayre syndrome (KSS), chronic progressive external ophthalmoplegia (CPEO), progressive external ophthalmoplegia (PEO), myoclonic epilepsy and ragged red fibers (MERRF), and mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS). Defective mitochondrial function caused by nuclear DNA mutations also leads to some mitochondrial genetic diseases. Mutations in OPA1, a mitochondrial dynamin-related guanosine triphosphatase (GTPase), have been demonstrated in patients with dominant optic atrophy (DOA), one of the most frequently occurring optic neuropathies. Friedreich's ataxia (FRDA) results from an abnormal GAA triplet repeat expansion in the first intron of the frataxin gene, resulting in decreased frataxin expression. Frataxin is a mitochondrial protein whose precise function remains unknown.
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