This disorder results from mutations in mitochondrial genes. Mitochondrial DNA has 16,500 basepairs and codes for 37 genes, many of which are involved in oxidative phosphorylation. For example, mutations in those that encode subunits of NADH dehydrogenase, MT-ND1, MT-ND2, MT-ND4, MT-ND5, and MT-ND6, are known to be responsible for LHON but at least 18 allelic variants are suspected to be causative.
Changes in basepairs located at base pairs 3460, 11778, and 14484 account for more than 90% of cases. In general, there is little clinical difference in the disease resulting from these mutations. The vision loss seems to be least among patients with mutations at bp 14484 and over 50% of patients recover some vision up to a year later. Those with mutations m.3460G>A and m.14484T>C are more likely to have some vision recovery. Mutations at bp 11778 tends to cause the most severe loss, especially in females.
The disorder is always inherited from the maternal side (males do not contribute mitochondria via their sperm). Many cases seem to arise de novo but in a majority of families there is a history of a similar disease among maternal relatives.
