TINF2

The TINF2 gene provides instructions for making part of the shelterin protein complex. This complex consists of a group of proteins that work together to help maintain structures known as telomeres, which are found at the ends of chromosomes. Telomeres help protect chromosomes from abnormally sticking together or breaking down (degrading).

The shelterin complex helps protect telomeres from the cell's DNA repair process. Without the protection of shelterin, the repair mechanism would sense the chromosome ends as abnormal breaks in the DNA sequence and either attempt to join the ends together or initiate cellular self-destruction (apoptosis).

dyskeratosis congenita - caused by mutations in the TINF2 gene

At least 15 mutations in the TINF2 gene have been identified in people with dyskeratosis congenita, including a severe form of this disorder called Revesz syndrome. Dyskeratosis congenita is characterized by changes in skin coloring (pigmentation), white patches inside the mouth (oral leukoplakia), and abnormally formed fingernails and toenails (nail dystrophy). People with dyskeratosis congenita have an increased risk of developing several life-threatening conditions, including cancer and a progressive lung disease called pulmonary fibrosis. Many affected individuals also develop a serious condition called aplastic anemia, which occurs when the bone marrow does not produce enough new blood cells.

Most of the TINF2 mutations that cause dyskeratosis congenita change single protein building blocks (amino acids) in the TINF2 protein, likely disrupting the function of the protein. The mutations result in dysfunction of the shelterin complex, interfering with its protection of telomeres and leading to reduced telomere length. Shortened telomeres can result in damage to genetic material, causing the cell to stop dividing or to self-destruct (undergo apoptosis).

Cells that divide rapidly are especially vulnerable to the effects of shortened telomeres. As a result, people with dyskeratosis congenita may experience a variety of problems affecting quickly dividing cells in the body such as cells of the nail beds, hair follicles, skin, lining of the mouth (oral mucosa), and bone marrow.

Breakage and instability of chromosomes resulting from inadequate telomere maintenance may lead to genetic changes that allow cells to divide in an uncontrolled way, resulting in the development of cancer in some people with dyskeratosis congenita.