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Leber hereditary optic neuropathy (LHON): a mitochondrial disease with unresolved complexities

Leber hereditary optic neuropathy, which seems to be the most common inherited eye disease, has, until recently, baffled investigators. Notwithstanding the finding of a mitochondrial DNA (mtDNA) mutation at nucleotide position (np) 11,778 by Wallace et al. (1988), there are still many questions to be answered. These include the relationship with diminished penetrance, the uneven sex distribution, the influence and nature of environmental factors, the possibility of additional (Xlinked?) genes, the importance of heteroplasmy, and the significance of the mitochondrial haplotype background.