Leber hereditary optic neuropathy

Leber s hereditary optic neuropathy (Leber optic atrophy)... 

Complex I deficiency due to mtDNA mutations (seven subunits of complex I are encoded by mtDNA) can be divided into encephalomyopathies and myopathies. The most important encephalomyopathy is Leber s hereditary optic neuropathy, characterized by acute or subacute loss of vision due to severe bilateral optic atrophy, with onset usually between 18 and 30 years and marked predominance in men. Three mutations (in ND1, ND4 and ND6)... 

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

Disease Example Leber Hereditary Optic Neuropathy... 

Leber s hereditary optic neuropathy (LHON) is caused by a mutation of the ND1 gene encoding an eie-ment of complex I of the eiectron transport chain and other simiiar mutations. 

LHON (Leber s hereditary optic neuropathy) causes blindness arising from mutations in the ND1 gene encoding complex I of the electron transport chain (see Chapter 7). 

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. 

D2. Danielson, S. R., Wong, A., Carelli, V., Martinuzzi, A., Schapira, A. H., and Cortopassi, G. A., Cells bearing mutations causing Leber s hereditary optic neuropathy are sensitized to Fas-induced apoptosis. J. Biol. Chem. 277, 5810-5815 (2002). 

V4. Vergani, L., Martinuzzi, A., Carelli, V., Cortelli, P., Montagna, P., Schievano, G., Carrozzo, R., Angelini, C., and Lugaresi, E., MtDNA mutations associated with Leber s hereditary optic neuropathy Studies on cytoplasmic hybrid (cybrid) cells. Biochem. Biophys. Res. Commun. 210, 880-888 (1995). 

MS), which is a demyelinating disorder. When optic neuritis occurs without disc swelling, the condition is called retrobulbar neuritis. When disc swelling is associated with optic neuritis, the condition is called papillitis. Papilledema is bilateral disc edema associated with increased intracranial pressure OCP). Optic atrophy, the end stage of many optic neuropathies, is characterized by a pale disc and associated with a relative afferent pupillary defect (RAPD) and possible loss of visual acuity, color vision, and visual field. One example of disc atrophy occurs in cases of Leber s hereditary optic neuropathy... 

Indications Alzheimer s dementia, cardiovascular disease, cerebrovascular disease, demyelination, depression, Friedreich s ataxia, improving memory, Leber s hereditary optic neuropathy Category Coenzyme Q10 analog Half-life N/A... 

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. ... 

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. 

Huoponen K, Puomiia A, Savontaus ML, Mustonen E, Kronqvist E, Nikoskelainen E. Genetic counseling in Leber hereditary optic neuropathy (LHON). Acta Ophthalmol Scand 2002 80 38-43. 

Mackey DA, Oostra RJ, Rosenberg T, Nikoskelainen E, Bronte-Stewart J, Poulton J, et al. Primary pathogenic mtDNA mutations in multigeneration pedigrees with Leber hereditary optic neuropathy Am J Hum Genet 1996 59 481-5. 

Man PYW, Turnbull DM, Chinnery PF. Leber hereditary optic neuropathy J Med Genet 2002 39 162-9. 

Muralidharan K. Detection of mitochondidal DNA mutations associated with Leber Hereditary Optic Neuropathy. Methods Molec Biol 2003 217 199-205. 

Newman NJ. From genotype to phenotype in Leber Hereditary Optic Neuropathy stiE more questions than answers. J Neuro-Ophthalmol 2002 22 257-61. 

Smith KH, Johns DR, Heher KL, Miller NR. Hetero-plasmy in Leber s hereditary optic neuropathy. Arch Ophthalmol 1993 111 1486-90. 

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