Leber's hereditary optic neuropathy. New genetic considerations
N. J. Newman
Department of Ophthalmology, Emory University School of Medicine, Atlanta, Ga.
OBJECTIVE--Leber's hereditary optic neuropathy (LHON) is a maternally
inherited disease that causes bilateral central visual loss, predominantly
in young men. Recently, this disorder has been associated with point
mutations in the mitochondrial genome. The clinical characteristics of LHON
are reviewed with special attention to recent advances in mitochondrial
genetics. DATA SOURCES--Literature from the mid-19th century to the present
is reviewed. STUDY SELECTION--Major review articles that include multiple
large pedigrees in their analysis are featured. Special emphasis is placed
on the recent reports on mitochondrial DNA abnormalities associated with
this disease. DATA EXTRACTION--The older literature is reviewed critically
with an understanding that some of the patients included as examples of
LHON may have had a different disease. The more current references are
assessed in regard to their inclusion of appropriate and complete
mitochondrial DNA analysis. DATA SYNTHESIS--Leber's hereditary optic
neuropathy, a maternally inherited disease primarily of young men, results
in bilateral, acute or subacute, central visual loss and, ultimately, optic
atrophy. Point mutations in the mitochondrial genes encoding proteins
essential to oxidative phosphorylation have been associated with this
disorder. Primary mutations include those found at positions 11778, 3460,
and, possibly, 15257 and 14484. Mitochondrial, nuclear, and environmental
factors may modify phenotypic expression. CONCLUSION--Genetic analysis has
allowed for a broader view of what constitutes the clinical phenotype of
LHON.
Leber's Hereditary Optic Neuropathy with Childhood Onset
Barboni et al.
IOVS 2006;47:5303-5309.
ABSTRACT
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Colour vision defects in asymptomatic carriers of the Leber's hereditary optic neuropathy (LHON) mtDNA 11778 mutation from a large Brazilian LHON pedigree: a case-control study
Quiros et al.
Br. J. Ophthalmol. 2006;90:150-153.
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Leber hereditary optic neuropathy with chorea and dementia resembling Huntington disease
Morimoto et al.
Neurology 2004;63:2451-2452.
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Chiasmal Enlargement and Optic Nerve Enhancement on Magnetic Resonance Imaging in Leber Hereditary Optic Neuropathy
Phillips et al.
Arch Ophthalmol 2003;121:577-579.
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Increase of mitochondrial DNA in blood cells of patients with Leber's hereditary optic neuropathy with 11778 mutation
Yen et al.
Br. J. Ophthalmol. 2002;86:1027-1030.
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Leber's hereditary optic neuropathy (LHON/11778) with myoclonus: report of two cases
Carelli et al.
J. Neurol. Neurosurg. Psychiatry 2001;71:813-816.
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The Other Human Genome
Shanske et al.
Arch Pediatr Adolesc Med 2001;155:1210-1216.
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Familial multisystem degeneration with parkinsonism associated with the 11778 mitochondrial DNA mutation
Simon et al.
Neurology 1999;53:1787-1787.
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A case of Leber's hereditary optic neuropathy with elevated blood levels of lactate and pyruvate
NINOMIYA et al.
Br. J. Ophthalmol. 1997;81:421c-421.
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Respiration and Growth Defects in Transmitochondrial Cell Lines Carrying the 11778 Mutation Associated with Leber's Hereditary Optic Neuropathy
Hofhaus et al.
J. Biol. Chem. 1996;271:13155-13161.
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Epidemic Optic Neuropathy in Cuba -- Clinical Characterization and Risk Factors
The Cuba Neuropathy Field Investigation Team
NEJM 1995;333:1176-1182.
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Mitochondrial DNA and Disease
Johns
NEJM 1995;333:638-644.
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