Leber hereditary optic neuropathy mitochondrial

Mutations in mtDNA are responsible for some cases of mitochondrial diseases, such as Leber hereditary optic neuropathy. 

MELAS, Mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes CPEO, chronic progressive external ophthalmoplegia LHON, Leber hereditary optic neuropathy NARP, neurogenic muscle weakness, ataxia, and retinitis pigmentosa NIDDM, non-insulin-dependent diabetes mellitus TER, termination. 

Leber hereditary optic neuropathy (LHON) is the most common mitochondrial disease and the first linked to maternal inheritance through a mutation in the mtDNA. LHON is characterized by bilateral subacute loss of central vision caused by focal degeneration of the retinal ganglion cell layer and of the optic nerve. After initial symptoms, both eyes are usually affected within 6 months. Approximately 50% to 60% of males and only 8% to 32% of females who possess the mtDNA mutation will actually develop this optic neuropathy. Nuclear-encoded factors that affect mtDNA expression, mtDNA products, or mitochondrial metabolism may modify the phenotypic expression of LHON. Genetic coimseling in LHON is complicated in that the amount of mutant mtDNA transmitted by heteroplasmic females cannot be predicted, and testing cannot predict which individuals will develop visual symptoms. ... 

Howell, N., etcd. (1991) Am. J. Hum. Genet. 49, 939-950. Leber hereditary optic neuropathy identification of the same mitochondrial NDl mutation in six pedigrees. 

Wallace DC, Singh G, Lott MT, et al. Mitochondrial DNA mutation associated with Leber s hereditary optic neuropathy. Science 1988 242(4884) 1427-1430. 

Fauser S, Leo-Kottler B, Besch D, Luberichs J. Confirmation of the 14568 mutation in the mitochondrial ND6 gene as causative in Leber s hereditary optic neuropathy. OpthaJ Genet 2002 23 191-7. 

Several diseases are caused by oxygen damage from the patient s own mitochondria, which are hot spots for ROS generation. In one of these diseases, Leber s hereditary optic neuropathy (LHON), the mitochondrial proteins that carry electrons and pump protons are broken. The first cells to die are the energy-burning optic nerve cells. The cells die because their broken mitochondria leak too many ROS. 

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