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 heparan sulfate. Heparan sulfate is a complex of sugar molecules (polysaccharide) that is added to proteins to form proteoglycans, which are proteins attached to several sugars. Heparan sulfate is involved in regulating a variety of body processes including blood clotting and the formation of blood vessels (angiogenesis). 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 are known as "loss-of-function" mutations, as they prevent any functional exostosin-1 protein from being made. The loss of exostosin-1 protein function prevents it from forming a complex with the exostosin-2 protein and adding heparan sulfate to proteins. It is unclear how this impairment leads to the signs and symptoms of hereditary multiple exostoses.

Langer-Giedion syndrome - associated with the EXT1 gene

The deletion or mutation of the EXT1 gene and at least one additional gene on chromosome 8 causes Langer-Giedion syndrome. These EXT1 gene mutations cause no exostosin-1 protein to be made. A lack of functional exostosin-1 protein causes the multiple noncancerous (benign) bone tumors (exostoses) seen in people with Langer-Giedion syndrome.

People with Langer-Giedion syndrome are always missing one functional copy of the EXT1 gene in each cell; however, other neighboring genes may also be involved. The deletion or mutation of additional genes near the EXT1 gene likely contributes to the varied features of this condition.