MT-RNR1

The MT-RNR1 gene provides instructions for making a particular type of RNA, a molecule that is a chemical cousin of DNA. This type of RNA, known as ribosomal RNA (rRNA), is involved in the assembly of proteins within cells.

The MT-RNR1 gene provides instructions for a specific form of ribosomal RNA called 12S RNA, which 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 and simple sugars to create adenosine triphosphate (ATP), the cell's main energy source. 12S RNA molecules help assemble protein building blocks (amino acids) into the functioning proteins that carry out oxidative phosphorylation.

nonsyndromic deafness - increased risk from variations of the MT-RNR1 gene

Several mutations in the MT-RNR1 gene can increase the risk of developing nonsyndromic deafness (hearing loss without related signs and symptoms affecting other parts of the body). If people with MT-RNR1 mutations are exposed to antibiotic medications known as aminoglycosides, they almost always develop permanent hearing loss within days to weeks of taking the medication. This group of antibiotics is typically used to treat chronic bacterial infections such as tuberculosis. Deafness resulting from exposure to these antibiotics is known as aminoglycoside ototoxicity.

Aminoglycosides treat infections by killing the bacteria that cause illness. These antibiotics are designed to kill bacteria by binding to their ribosomal RNA and disrupting the bacteria's ability to make proteins. Most mutations in the MT-RNR1 gene change single building blocks (nucleotides) in the 12S RNA molecule, which often makes the human 12S RNA look very similar to bacterial ribosomal RNA. As a result, aminoglycosides can target the 12S RNA molecule in human cells just as they target bacterial ribosomal RNA. The antibiotic easily binds to the abnormal 12S RNA, which impairs the ability of mitochondria to produce proteins needed for oxidative phosphorylation. Researchers believe that this unintended effect of aminoglycosides may reduce the amount of ATP produced in mitochondria, increase the production of harmful byproducts, and eventually cause the cell to self-destruct (undergo apoptosis). It is unknown why damage caused by aminoglycosides is often limited to cells in the inner ear that are essential for hearing.

Some people with mutations in the MT-RNR1 gene experience hearing loss even if they are never exposed to aminoglycosides. In these cases, problems with hearing usually begin in early adulthood. Studies suggest that other genetic and environmental factors play an important role in determining whether people with changes in the MT-RNR1 gene will develop hearing loss.