MT-TH

The MT-TH gene provides instructions for making a particular type of RNA, a molecule that is a chemical cousin of DNA. This type of RNA, called transfer RNA (tRNA), helps assemble protein building blocks known as amino acids into full-length, functioning proteins. The MT-TH gene provides instructions for a specific form of tRNA that is designated as tRNA^His. This molecule attaches to a particular amino acid, histidine (His), and inserts it into the appropriate locations in many different proteins.

The tRNA^His molecule is present only in cellular structures called mitochondria. These structures convert energy from food into a form that cells can use. Through a process called oxidative phosphorylation, mitochondria use oxygen, simple sugars, and fatty acids to create adenosine triphosphate (ATP), the cell's main energy source. The tRNA^His molecule is involved in the assembly of proteins that carry out oxidative phosphorylation.

mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes - caused by mutations in the MT-TH gene

A small number of people with the features of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) have been identified with a mutation in the MT-TH gene. These individuals also have some features of another mitochondrial disorder, myoclonic epilepsy with ragged-red fibers (MERRF). This combination of signs and symptoms is called MERRF/MELAS overlap syndrome. The features of this syndrome that are consistent with MELAS include recurrent severe headaches, muscle weakness (myopathy), hearing loss, stroke-like episodes including a loss of consciousness, seizures, and other problems affecting the nervous system. The signs and symptoms of MERRF/MELAS overlap syndrome appear in early adulthood.

A particular mutation in the MT-TH gene appears to be responsible for MERRF/MELAS overlap syndrome. This mutation changes a single DNA building block (nucleotide) in the gene. Specifically, it replaces the nucleotide guanine with the nucleotide adenine at gene position 12147 (written as G12147A). Researchers have not determined how this genetic change alters energy production in mitochondria or causes the varied signs and symptoms of the MERRF/MELAS overlap syndrome.

myoclonic epilepsy with ragged-red fibers - caused by mutations in the MT-TH gene

As mentioned above, a few individuals with the G12147A mutation in the MT-TH gene have features of myoclonic epilepsy and ragged red fibers (MERRF) and MELAS. The signs and symptoms of MERRF/MELAS overlap syndrome that are consistent with MERRF include muscle twitches (myoclonus), muscle weakness (myopathy), difficulty coordinating movement (ataxia), hearing loss, and seizures. It remains unknown why this mutation causes the overlapping features of MERRF and MELAS.

other disorders - associated with the MT-TH gene

Another mutation in the MT-TH gene may increase the risk of developing a heart condition called cardiomyopathy. People with cardiomyopathy have weakened heart muscle that is unable to pump blood effectively. A particular change in the MT-TH gene has been identified in several adults with cardiomyopathy, but without other common signs of mitochondrial disease such as neurological abnormalities. This mutation replaces the nucleotide guanine with the nucleotide adenine at gene position 12192 (written as G12192A). It is unclear why this alteration in mitochondrial DNA may increase a person's risk of developing heart problems without affecting other parts of the body.