methionine to valine. The T14484C mutation is associated with a good long-term prognosis; affected people with this genetic change have a 37 percent to 65 percent chance of some visual recovery. Researchers are investigating how mutations in the MT-ND6 gene lead to Leber's hereditary optic neuropathy. These genetic changes appear to prevent Complex I from interacting normally with ubiquinone, which may affect the generation of ATP and may also increase the production within mitochondria of potentially harmful molecules called reactive oxygen species (ROS). 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. A G → A mutation at the 14459 base pair in the MT-ND6 gene also has been identified in a small number of people with Leigh's syndrome, a progressive brain disorder that typically appears in infancy or early childhood. Affected children may experience vomiting, seizures, delayed development, muscle weakness, and problems with movement. Heart disease, kidney problems, and difficulty breathing can also occur in people with this disorder. This MT-ND6 G14459A mutation replaces the amino acid alanine with the amino acid valine at protein position 72 in the NADH-ubiquinone oxidoreductase chain 6 protein. This genetic change also has been found in people with LHON and a movement disorder called dystonia, which involves involuntary muscle contractions, tremors, and other uncontrolled movements. This mutation appears to disrupt the normal assembly or activity of complex I in mitochondria. It is not known, however, how this MT-ND6 gene alteration is related to the specific features of Leigh syndrome, LHON, or dystonia. It also remains unclear why a single mutation can cause such varied signs and symptoms in different people. Interactions MT-ND6 interacts with the NADH dehydrogenase [ubiquinone] iron-sulfur protein 3 (NDUFS3) and the ATP-dependent metalloprotease YME1L1. References Further reading External links Mass spectrometry characterization of MT-ND6 at COPaKB GeneReviews/NCBI/NIH/UW entry on Mitochondrial DNA-Associated Leigh Syndrome and NARP Proteins Human mitochondrial genes