EXT2

The EXT2 gene provides instructions for producing a protein called exostosin-2. 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-2 attaches (binds) to another protein, exostosin-1, 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 EXT2 gene

More than 90 mutations in the EXT2 gene have been identified in people with hereditary multiple exostoses type 2, a condition in which people develop multiple benign (noncancerous) bone tumors called exostoses. Most of these mutations prevent any functional exostosin-2 protein from being made, and are called "loss-of-function" mutations. The loss of exostosin-2 protein function prevents it from forming a complex with the exostosin-1 protein and modifying heparan sulfate. It is unclear how this impairment leads to the signs and symptoms of hereditary multiple exostoses.

Potocki-Shaffer syndrome - caused by mutations in the EXT2 gene

A mutation resulting in the deletion of the EXT2 gene causes a condition called Potocki-Shaffer syndrome. People with this condition have multiple exostoses (described above) and enlarged openings in two bones that make up much of the top and sides of the skull (enlarged parietal foramina). Other signs and symptoms seen in some people with Potocki-Shaffer syndrome include intellectual disability, developmental delay, distinctive facial features, vision problems, and defects in the heart, kidneys, and urinary tract.

Potocki-Shaffer syndrome (sometimes referred to as proximal 11p deletion syndrome) is caused by a deletion of genetic material from the short (p) arm of chromosome 11. In people with this condition, a loss of the EXT2 gene within this region is responsible for multiple exostoses. The deletion likely leads to a reduction of exostosin-2 protein and the inability to process heparan sulfate correctly. Although heparan sulfate is involved in many body processes, it is unclear how the lack of this protein causes multiple exostoses. The loss of another gene, ALX4, in the same region of chromosome 11 underlies the defects in skull development. The loss of additional genes in the deleted region likely contributes to the other features of Potocki-Shaffer syndrome.