NBN

At least 10 mutations in the NBN gene have been found to cause Nijmegen breakage syndrome, a condition characterized by slow growth, recurrent infections, and an increased risk of developing cancer. The NBN gene mutations that cause Nijmegen breakage syndrome typically lead to the production of an abnormally short version of the nibrin protein. The mutation found in most affected individuals, particularly in Slavic populations of Eastern Europe, deletes five DNA building blocks (nucleotides) from the NBN gene (written as 657_661del5). This mutation leads to the production of a shortened version of the nibrin protein called p70-nibrin. This shortened protein is not as effective as normal nibrin in responding to DNA damage, but p70-nibrin does appear to have some residual function.

When breaks in DNA are not repaired properly, genetic damage can accumulate. A buildup of errors in DNA can trigger cells to grow and divide abnormally, increasing the risk of cancer in people with Nijmegen breakage syndrome. Nibrin's role in regulating cell division and cell growth (proliferation) is thought to lead to the problems with the immune system that are seen in affected individuals. A lack of functional nibrin results in less immune cell proliferation. A decrease in the amount of immune cells that are produced leads to a malfunctioning immune system. It is unclear how mutations in the NBN gene cause the other features of Nijmegen breakage syndrome.

Inherited mutations in the NBN gene, including the c.657_661del5 mutation described above, have also been associated with several other types of cancer. Studies in Eastern European populations reported that people with mutations in one copy of the NBN gene in each cell may be more likely to develop breast cancer than people who do not carry NBN mutations. Cells with a mutation in one copy of the NBN gene do not repair DNA as effectively as cells without these mutations. It is thought that DNA damage accumulates over time, which can trigger cells to grow and divide uncontrollably and increase the risk of developing cancer.

Inherited mutations in the NBN gene, including the c.657_661del5 mutation described above, have also been associated with several other types of cancer. Studies in Eastern European populations reported that people with mutations in one copy of the NBN gene in each cell may be more likely to develop ovarian cancer than people who do not carry NBN mutations. Cells with a mutation in one copy of the NBN gene do not repair DNA as effectively as cells without these mutations. It is thought that DNA damage accumulates over time, which can trigger cells to grow and divide uncontrollably and increase the risk of developing cancer.

Inherited mutations in the NBN gene, including the c.657_661del5 mutation described above, have also been associated with several other types of cancer. Studies in Eastern European populations reported that people with mutations in one copy of the NBN gene in each cell may be more likely to develop prostate cancer than people who do not carry NBN mutations. Cells with a mutation in one copy of the NBN gene do not repair DNA as effectively as cells without these mutations. It is thought that DNA damage accumulates over time, which can trigger cells to grow and divide uncontrollably and increase the risk of developing cancer.

Inherited mutations in the NBN gene, including the c.657_661del5 mutation described above, have also been associated with several other types of cancer. Studies in Eastern European populations reported that people with mutations in one copy of the NBN gene in each cell may be more likely to develop an aggressive form of skin cancer (melanoma) or cancer of blood-forming cells (leukemia) than people who do not carry NBN mutations. Cells with a mutation in one copy of the NBN gene do not repair DNA as effectively as cells without these mutations. It is thought that DNA damage accumulates over time, which can trigger cells to grow and divide uncontrollably and increase the risk of developing cancer.