2.1. Leber hereditary optic neuropathy

Several mutations in the MT-ND1 gene are known to cause Leber hereditary optic neuropathy. Each of these mutations changes a single DNA building block (nucleotide) in the gene. One common MT-ND1 mutation is responsible for about 13 percent of all cases of Leber hereditary optic neuropathy. This mutation replaces the nucleotide guanine with the nucleotide adenine at gene position 3460 (written as G3460A). This change is associated with moderately severe cases of Leber hereditary optic neuropathy; however, 20 percent to 40 percent of people with vision loss due to this mutation experience some recovery of vision.

Researchers are investigating how mutations in the MT-ND1 gene lead to Leber hereditary optic neuropathy. These genetic changes appear to disrupt the normal activity of complex I in the mitochondrial inner membrane, which may affect the generation of ATP. MT-ND1 mutations also may increase the production within mitochondria of potentially harmful molecules called reactive oxygen species. It remains unclear, however, why the effects of these mutations are often limited to the nerve that relays visual information from the eye to the brain (the optic nerve). Additional genetic and environmental factors probably contribute to the vision loss and other medical problems associated with Leber hereditary optic neuropathy.

2.2. Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes

MT-ND1 mutations are a rare cause of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS). Most cases of MELAS are caused by mutations in other mitochondrial genes, but a small number of cases resulting from mutations in the MT-ND1 gene have been reported. Fewer than five mutations, each of which alters a single DNA building block (nucleotide) in the gene, have been identified in affected individuals. These genetic changes reduce the activity of complex I, which disrupts energy production within mitochondria. Although these abnormalities have the greatest impact on tissues that require a lot of energy (such as the brain and muscles), researchers have not determined how changes in the MT-ND1 gene lead to the specific signs and symptoms of MELAS.

2.3. Other disorders

A mutation in the MT-ND1 gene has been reported in a few cases of adult-onset dystonia. Dystonia is a movement disorder that involves involuntary tensing of the muscles (muscle contractions), tremors, and other uncontrolled movements. The MT-ND1 mutation associated with these rare cases replaces the nucleotide adenine with the nucleotide guanine at gene position 3796 (written as A3796G). Further studies are needed to determine whether this genetic change combines with other genetic and environmental factors to increase the risk of developing adult-onset dystonia.