TREX1

Variants (also called mutations) in the TREX1 gene have been identified in people with Aicardi-Goutières syndrome, a disorder that involves severe brain dysfunction (encephalopathy), skin lesions, and other health problems. Most of these variants are believed to prevent the production of the three prime repair exonuclease 1 enzyme. Researchers suggest that the absence of this enzyme allows unneeded DNA and RNA to accumulate in cells. These DNA and RNA molecules may be mistaken by cells for the genetic material of viral invaders. This likely triggers immune system reactions that damage the brain, skin, and other organs, resulting in the signs and symptoms of Aicardi-Goutières syndrome.

Variants in the TREX1 gene have also been identified in people with a chronic inflammatory disease called systemic lupus erythematosus (SLE). People with TREX1 gene variants may develop a rare form of SLE called chilblain lupus that mainly affects the skin. Signs and symptoms of chilblain lupus include joint pain and painful skin lesions on the fingers, ears, nose, toes, and cheeks that worsen in the cold. Features of chilblain lupus often occur in people with Aicardi-Goutières syndrome (described above). Variants in the TREX1 gene likely prevent the cell from producing functioning versions of the three prime repair exonuclease 1 enzyme. Without this enzyme, the immune system doesn’t function properly, leading to the signs and symptoms of SLE.

TREX1 gene variants have also been found in people with a disorder called autosomal dominant retinal vasculopathy with cerebral leukodystrophy, which affects the brain and the blood vessels in the specialized light-sensitive tissue that lines the back of the eye (the retina). As in people with Aicardi-Goutières syndrome, the absence or impaired function of the three prime repair exonuclease 1 enzyme may cause immune system dysfunction that damages the brain, skin, blood vessels, and other parts of the body.

Variants in the TREX1 gene can also cause a condition called cryofibrinogenemia. This is a rare blood disorder where the blood plasma in certain parts of the body can become much colder than normal (sometimes near freezing). As a result, the skin in the affected area can have a bluish tint or develop lesions from lack of blood flow. The areas most commonly affected in people with cryofibrinogenemia are the hands, feet, ears, nose, and buttocks.