XPA
XPA, DNA damage recognition and repair factor
Normal Function
Health Conditions Related to Genetic Changes
Xeroderma pigmentosum
Many variants (also called mutations) in the XPA gene have been found to cause xeroderma pigmentosum. People with this condition have an extreme sensitivity to UV rays from sunlight. As a result, affected individuals have a high risk of sunlight-induced cancer and premature aging.
XPA gene variants are responsible for a very severe form of xeroderma pigmentosum that is more common in the Japanese population than in other populations. Most Japanese people with xeroderma pigmentosum have the same XPA gene variant, which is written as IVS3AS, G>C. This variant prevents cells from producing any functional XPA protein. Other XPA gene variants, which have been reported in Japan and elsewhere, result in the production of a nonfunctional version of the XPA protein or greatly reduce the amount of this protein that is made in cells.
A partial or total loss of the XPA protein prevents cells from repairing DNA damage normally. As damage builds up in DNA, cells malfunction and eventually become cancerous or die. These problems with DNA repair cause people with xeroderma pigmentosum to be extremely sensitive to UV rays. When UV rays damage genes that control cell growth and division, cells can grow too fast and in an uncontrolled way. This uncontrolled cell growth can lead to cancer. In people with xeroderma pigmentosum, these cancers occur most frequently in areas of the body that are exposed to the sun, such as the skin and eyes.
When xeroderma pigmentosum is caused by XPA gene variants, it is often associated with progressive neurological abnormalities. These nervous system problems include hearing loss, poor coordination, difficulty walking, movement problems, loss of intellectual function, difficulty swallowing and talking, and seizures. The neurological abnormalities are thought to result from a buildup of DNA damage, although the brain is not exposed to UV rays. Researchers suspect that other factors damage DNA in nerve cells. It is unclear why some people with xeroderma pigmentosum develop neurological abnormalities and others do not.
More About This Health ConditionRelated Conditions
Xeroderma pigmentosum
Health Conditions Related to Genetic Changes
Many variants (also called mutations) in the XPA gene have been found to cause xeroderma pigmentosum. People with this condition have an extreme sensitivity to UV rays from sunlight. As a result, affected individuals have a high risk of sunlight-induced cancer and premature aging.
XPA gene variants are responsible for a very severe form of xeroderma pigmentosum that is more common in the Japanese population than in other populations. Most Japanese people with xeroderma pigmentosum have the same XPA gene variant, which is written as IVS3AS, G>C. This variant prevents cells from producing any functional XPA protein. Other XPA gene variants, which have been reported in Japan and elsewhere, result in the production of a nonfunctional version of the XPA protein or greatly reduce the amount of this protein that is made in cells.
A partial or total loss of the XPA protein prevents cells from repairing DNA damage normally. As damage builds up in DNA, cells malfunction and eventually become cancerous or die. These problems with DNA repair cause people with xeroderma pigmentosum to be extremely sensitive to UV rays. When UV rays damage genes that control cell growth and division, cells can grow too fast and in an uncontrolled way. This uncontrolled cell growth can lead to cancer. In people with xeroderma pigmentosum, these cancers occur most frequently in areas of the body that are exposed to the sun, such as the skin and eyes.
When xeroderma pigmentosum is caused by XPA gene variants, it is often associated with progressive neurological abnormalities. These nervous system problems include hearing loss, poor coordination, difficulty walking, movement problems, loss of intellectual function, difficulty swallowing and talking, and seizures. The neurological abnormalities are thought to result from a buildup of DNA damage, although the brain is not exposed to UV rays. Researchers suspect that other factors damage DNA in nerve cells. It is unclear why some people with xeroderma pigmentosum develop neurological abnormalities and others do not.