MT-TL1

The MT-TL1 gene provides instructions for making a molecule that is a chemical cousin of DNA. This molecule, called a transfer RNA (tRNA), helps assemble protein building blocks known as amino acids into functioning proteins. The MT-TL1 gene provides instructions for making a specific form of transfer RNA that is designated as tRNA^Leu(UUR). During protein assembly, this molecule attaches to the amino acid leucine (Leu) and inserts it into the appropriate locations in the protein.

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

mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes - caused by mutations in the MT-TL1 gene

Several mutations in the MT-TL1 gene have been identified in people with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS). Most of these mutations change single DNA building blocks (nucleotides) in the gene. The most common mutation, A3243G, is responsible for about 80 percent of all MELAS cases. This genetic change replaces the nucleotide adenine with the nucleotide guanine at position 3243 in the MT-TL1 gene. The A3243G mutation impairs the ability of mitochondria to make proteins, use oxygen, and produce energy. Researchers have not determined how changes in mitochondrial DNA lead to the specific signs and symptoms of MELAS. They continue to investigate the effects of mitochondrial gene mutations in different tissues, particularly in the brain.

other disorders - associated with the MT-TL1 gene

About 20 mutations in the MT-TL1 gene have been reported, most of which change single nucleotides in the gene. These mutations are associated with a variety of signs and symptoms chiefly affecting the muscles and nervous system. People with MT-TL1 mutations often have muscle weakness, pain, and extreme fatigue, particularly during exercise (exercise intolerance). In some cases, the heart muscle is also weakened, preventing the heart from pumping as it should. Additionally, mutations in the MT-TL1 gene are frequently responsible for an eye condition called progressive external ophthalmoplegia (PEO). This disorder weakens the muscles that control eye movement and causes the eyelids to droop (ptosis).

A few children with changes in the MT-TL1 gene have experienced delayed development, psychiatric problems, or developmental disorders that affect communication and social interaction (autistic spectrum disorders). MT-TL1 mutations also have been identified in a small number of cases of sudden infant death syndrome (SIDS), which is a major cause of death in babies younger than one year.

The A3243G mutation, which typically causes MELAS, is also associated with a condition called maternally inherited diabetes and deafness. Most people with this MT-TL1 mutation develop diabetes in adulthood, usually in their mid-thirties. Many also experience hearing loss, particularly at high tones. Less commonly, heart problems and kidney failure are associated with this condition. Researchers believe that the A3243G mutation impairs the function of certain cells in the pancreas. These cells, known as beta cells, normally produce a hormone called insulin that helps control blood sugar levels. Diabetes results when the beta cells do not produce enough insulin to regulate blood sugar effectively. Researchers have not determined how the A3243G mutation leads to hearing loss or the other medical problems associated with maternally inherited diabetes and deafness.