MT-ND6

Several variants (also called mutations) in the MT-ND6 gene have been identified in people with Leber hereditary optic neuropathy. This condition is an inherited form of vision loss. Each of the MT-ND6 gene variants changes a single protein building block (amino acid) in the NADH dehydrogenase 6 protein. One common MT-ND6 gene variant is responsible for about 14 percent of all cases of Leber hereditary optic neuropathy, and it is the most common cause of this disorder among people of French Canadian descent. This genetic change, written as T14484C or Met64Val, replaces the amino acid methionine with the amino acid valine at protein position 64.  The T14484C variant 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 variants in the MT-ND6 gene lead to Leber hereditary optic neuropathy.  These genetic changes appear to prevent complex I from interacting normally with ubiquinone, which may affect the generation of ATP. 

Variants another gene called MT-ND4 may also increase the production within mitochondria of potentially harmful molecules called reactive oxygen species. It remains unclear, however, why the effects of these variants 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 variant in the MT-ND6 gene also has been identified in a small number of people with Leigh 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 Leigh syndrome.

The MT-ND6 gene variant that can cause Leigh syndrome, written as G14459A or Ala72Val, replaces the amino acid alanine with the amino acid valine at protein position 72. This genetic change also has been found in people with Leber hereditary optic neuropathy and a movement disorder called dystonia, which involves involuntary muscle contractions, tremors, and other uncontrolled movements.  This variant 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, Leber hereditary optic neuropathy, or dystonia.  It also remains unclear why a single variant can cause such varied signs and symptoms in different people.

MedlinePlus Genetics provides information about Mitochondrial complex I deficiency