SHOX

The SHOX gene provides instructions for making a protein that regulates the activity of other genes. On the basis of this role, the SHOX protein is called a transcription factor. The SHOX gene is part of a larger family of homeobox genes, which act during early embryonic development to control the formation of many body structures. Specifically, the SHOX protein is essential for the development of the skeleton. It plays a particularly important role in the growth and maturation of bones in the arms and legs.

One copy of the SHOX gene is located on each of the sex chromosomes (the X and Y chromosomes) in an area called the pseudoautosomal region. Although many genes are unique to the X or Y chromosome, genes in the pseudoautosomal region are present on both chromosomes. As a result, women (who have two X chromosomes) and men (who have one X and one Y chromosome) each have two functional copies of the SHOX gene in each cell.

Turner syndrome - associated with the SHOX gene

Turner syndrome occurs when one normal X chromosome is present in a female's cells and the other sex chromosome is missing or structurally altered. Because the SHOX gene is located on the X chromosome, most women with Turner syndrome have only one copy of the gene in each cell instead of the usual two copies. Loss of one copy of this gene reduces the amount of SHOX protein by half. Researchers believe that a shortage of this protein is at least partly responsible for short stature and skeletal abnormalities (such as unusual rotation of the wrist and elbow joints) in women with this condition.

other disorders - caused by mutations in the SHOX gene

Changes involving the SHOX gene are responsible for several skeletal disorders characterized by short stature. People with Leri-Weill dyschondrosteosis have short bones in the forearm and lower leg and an abnormality of the wrist bones called Madelung deformity. Another disorder, Langer mesomelic dysplasia, has signs and symptoms that are similar to those of Leri-Weill dyschondrosteosis but are more severe. The major features of Langer mesomelic dysplasia include shortening of the long bones of the arms and legs (particularly in the forearm and lower leg) and mild underdevelopment of the lower jaw bone (mandible). Madelung deformity is usually not seen with Langer mesomelic dysplasia.

Mutations in or near one copy of the SHOX gene in each cell cause Leri-Weill dyschondrosteosis, while mutations in both copies of the gene cause the more severe Langer mesomelic dysplasia. These mutations reduce the amount of SHOX protein or prevent the production of any of this protein. A shortage of SHOX protein leads to the skeletal abnormalities characteristic of these disorders.

Deletions of the entire SHOX gene or mutations within the gene have also been identified in some people with short stature. This short stature is usually described as idiopathic, which means it is not associated with the characteristic features of a disease or syndrome. Some people with short stature and change in the SHOX gene have been found to have subtle skeletal abnormalities, however.