Leber s hereditary optic neuropathy

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. 

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). 

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). 

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

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... 

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. 

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

Mildly deleterious base substitutions 2. Moderately deleterious nucleotide substitutions 3. Severe nucleotide substitutions Familial deafness, Alzheimer s disease, Parkinson s disease Leber s Hereditary Optic Neuropathy (LHON), Myoclonic Epilepsy and Ragged-Red Fiber disease (MERRF) Leigh s Syndrome dystonia... 

Like the mitochondria themselves, some genetic diseases of energy metabolism are maternally inherited. One such disease, Leber s hereditary optic neuropathy (LHON), causes blindness and heart problems. People with LHON have a reduced ability to make ATP. As a result, sensitive tissues that demand a great deal of energy eventually die. LHON sufferers eventually lose their sight because the optic nerve dies from lack of energy. 

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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