MPV17

More than 30 mutations in the MPV17 gene have been found to cause MPV17-related hepatocerebral mitochondrial DNA depletion syndrome, a condition characterized by liver disease and neurological problems that begin in infancy. Most of the mutations that cause this condition change single protein building blocks (amino acids) in the MPV17 protein. One mutation that almost exclusively affects the Navajo population of the southwestern United States replaces the amino acid arginine with the amino acid glutamine at position 50 in the protein (written as R50Q). This mutation results in the production of an unstable MPV17 protein that is quickly broken down. When the condition occurs in people of Navajo ancestry, it is called Navajo neurohepatopathy.

The changes in the MPV17 protein that cause MPV17-related hepatocerebral mitochondrial DNA depletion syndrome, including the R50Q mutation, impair protein function and reduce the amount of protein that is available. A dysfunctional or absent MPV17 protein leads to problems with the maintenance of mtDNA, which can cause a reduction in the amount of mtDNA (known as mitochondrial DNA depletion). Mitochondrial DNA depletion impairs mitochondrial function in many of the body's cells and tissues, particularly the brain, liver, and other tissues that have high energy requirements. Reduced mitochondrial function in the liver and brain lead to the liver failure and neurological dysfunction associated with MPV17-related hepatocerebral mitochondrial DNA depletion syndrome. Researchers suggest that the less mtDNA that is available in cells, the more severe the features of Navajo neurohepatopathy.

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