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Leber hereditary optic neuropathy
MIM.535000
Thursday 25 September 2003
The predilection for Leber hereditary optic neuropathy (LHON) to develop in young men is explained by inheritance of mitochondrial gene mutations (mtDNA mutations).
It is possible that these mutations provide for a genetic susceptibility to a variety of environmental exposures that constitute the final trigger for optic nerve degeneration.
Studies of an epidemic of blindness in Cuba affecting 50,000 patients suggested acquired impairment of mitochondrial function through exposure to toxins, low folate, and high formic acid levels. These patients developed a syndrome that is phenotypically similar to LHON.
The factor common to these optic neuropathies-inherited or acquired-appears to be a derangement in mitochondrial function. Since neuronal health is dependent on axoplasmic transport of mitochondria, mitochondrial dysfunctions give rise to neurologic disorders.
Etiology
mitochondrial DNA mutations at nucleotide (nt) 3460, 11778, or 14484 (classic LHON mutations)
candidate pathogenic mitochondrial DNA mutations at nts 9804, 13051, and 14325 (12736867)
germline mutations in gene RDH12 coding for retinal dehydrogenase 12 (15322982)
References
Preising MN, Heegard S. Recent advances in early-onset severe retinal degeneration: more than just basic research. Trends Mol Med. 2004 Feb;10(2):51-4. PMID: 15106616
