EXT1

About 480 mutations in the EXT1 gene have been identified in people with hereditary multiple osteochondromas type 1, a condition in which people develop multiple benign (noncancerous) bone tumors called osteochondromas. Most of these mutations are known as "loss-of-function" mutations because they prevent any functional exostosin-1 protein from being made. The loss of functional exostosin-1 protein 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 osteochondromas.

The EXT1 gene is located in a region of chromosome 8 that is deleted in people with trichorhinophalangeal syndrome type II (TRPS II). TRPS II is a condition that causes bone and joint malformations including multiple osteochondromas (described above); distinctive facial features; intellectual disability; and abnormalities of the skin, hair, teeth, sweat glands, and nails. As a result of this deletion, affected individuals are missing one copy of the EXT1 gene in each cell. A shortage of exostosin-1 protein causes the osteochondromas in people with TRPS II. The deletion of other genes near the EXT1 gene likely contributes to the additional features of this condition.