EXT1

The EXT1 gene provides instructions for producing a protein called exostosin-1. This protein is found in a cell structure called the Golgi apparatus, which modifies newly produced enzymes and other proteins. In the Golgi apparatus, exostosin-1 attaches (binds) to another protein, exostosin-2, to form a complex that modifies a protein called heparan sulfate so it can be used in the body. Heparan sulfate is involved in regulating a variety of body processes including the formation of blood vessels (angiogenesis) and blood clotting. It also has a role in the spreading (metastasis) of cancer cells.

hereditary multiple exostoses - caused by mutations in the EXT1 gene

About 200 mutations in the EXT1 gene have been identified in people with hereditary multiple exostoses type 1. Most of these mutations prevent any functional exostosin-1 protein from being made, and are known as "loss of function" mutations. The loss of exostosin-1 protein function prevents it from forming a complex with the exostosin-2 protein and modifying heparan sulfate. It is unclear how this impairment leads to the signs and symptoms of hereditary multiple exostoses.

other disorders - caused by mutations in the EXT1 gene

A mutation that results in the deletion of the EXT1 gene causes a condition called Langer-Giedion syndrome. In addition to multiple exostoses, people with this condition have distinctive facial features that include sparse scalp hair, a rounded nose, a long flat area between the nose and the upper lip (philtrum), and a thin upper lip. Affected individuals also have short stature and the ends of their long bones (epiphyses) are cone-shaped.

Langer-Giedion syndrome (sometimes referred to as trichorhinophalangeal syndrome, type II) is often described as a contiguous gene deletion syndrome because it results from the loss of several genes that are close together on chromosome 8. Researchers have determined that the loss of EXT1 is responsible for the multiple exostoses seen in people with Langer-Giedion syndrome. The loss of another gene, TRPS1, in the same region of chromosome 8 may help explain the facial abnormalities. Additional genes in the deleted region likely contribute to the varied features of Langer-Giedion syndrome.