The NBN gene is involved in the repair of DNA damage, specifically double-strand breaks, which are one of the most serious types of DNA damage. Mutations in the NBN gene have been linked to an increased risk of certain types of cancer, as well as a rare genetic disorder called Nijmegen breakage syndrome (NBS).
What is the NBN gene?
The NBN gene, also known as NBS1, is located on chromosome 8q21 and encodes a protein called nibrin. Nibrin is part of a protein complex called MRN (Mre11-Rad50-Nbs1), which is involved in the detection and repair of DNA damage, specifically double-strand breaks.
Double-strand breaks occur when both strands of the DNA molecule are broken, and this can happen as a result of exposure to ionizing radiation, chemicals, or other environmental factors. If left unrepaired, double-strand breaks can lead to cell death or mutations, which can lead to cancer.
The MRN complex helps to detect double-strand breaks and recruit other proteins to the site of the damage to repair it. Nibrin, in particular, is important for regulating the activity of another protein called ATM (ataxia-telangiectasia mutated), which is also involved in the repair of double-strand breaks.
What are NBN gene mutations?
Mutations in the NBN gene can affect the function of the MRN complex and lead to problems with DNA repair. There are several different types of NBN gene mutations, including:
Frameshift mutations: These types of mutations occur when one or more nucleotides (the building blocks of DNA) are inserted or deleted from the DNA sequence, which changes the reading frame of the gene. This can result in a truncated protein or a nonfunctional protein.
Missense mutations: These types of mutations occur when a single nucleotide is changed, which can result in an amino acid substitution in the protein. Depending on the position of the mutation, this can affect the function of the protein.
Nonsense mutations: These types of mutations occur when a premature stop codon is introduced in the protein-coding sequence, resulting in a truncated protein.
Splice site mutations: These types of mutations occur at the junctions between exons and introns, which can affect the splicing of the mRNA transcript and result in an altered protein.
Large deletions: These types of mutations involve the loss of a large portion of the DNA sequence, which can result in a nonfunctional protein.
Nijmegen breakage syndrome (NBS)
Nijmegen breakage syndrome (NBS) is a rare genetic disorder that is caused by mutations in the NBN gene. It is characterized by growth retardation, microcephaly (a small head size), immunodeficiency, and an increased susceptibility to cancer.
People with NBS have a defective MRN complex, which leads to problems with DNA repair. They are particularly sensitive to ionizing radiation, which can cause additional DNA damage and increase their risk of developing cancer.
The most common types of cancer associated with NBS are lymphomas and leukemias, which typically develop at a young age (before the age of 20). Other types of cancer that have been reported in individuals with NBS include breast cancer, brain tumors, and sarcomas.
Because NBS is a rare disorder, it is often misdiagnosed or undiagnosed. However, early diagnosis is important for appropriate management and surveillance for cancer.
Cancer risk associated with NBN gene mutations
In addition to NBS, mutations in the NBN gene have been linked to an increased risk of certain types of cancer in the general population. These include:
Breast cancer: Studies have shown that women with NBN gene mutations have an increased risk of developing breast cancer, particularly at a young age (before the age of 50). The risk is thought to be higher for certain subtypes of breast cancer, such as triple-negative breast cancer.
Prostate cancer: Some studies have suggested that NBN gene mutations may be associated with an increased risk of prostate cancer, particularly in men with a family history of the disease.
Lung cancer: A small number of studies have suggested that NBN gene mutations may be associated with an increased risk of lung cancer, particularly in smokers.
Other types of cancer that have been reported in individuals with NBN gene mutations include leukemia, lymphoma, ovarian cancer, and colorectal cancer. However, these associations are less well-established and require further study.
Testing for NBN gene mutations
Testing for NBN gene mutations can be useful for individuals with a family history of NBS or a personal history of cancer, particularly at a young age. It can also be used for carrier testing in individuals with a family history of NBS.
Testing typically involves sequencing the entire coding region of the NBN gene to identify mutations. However, not all mutations in the NBN gene are associated with an increased risk of cancer, so it is important to interpret the results in the context of the individual’s personal and family history.
Management of individuals with NBN gene mutations
Management of individuals with NBN gene mutations depends on the specific mutation and the individual’s personal and family history of cancer. Generally, individuals with NBN gene mutations should receive regular surveillance for cancer, including breast MRI and mammography for women and prostate-specific antigen testing for men.
Risk-reducing strategies, such as prophylactic mastectomy or oophorectomy for women with a high risk of breast or ovarian cancer, may also be considered in certain cases.
In addition, individuals with NBN gene mutations may benefit from lifestyle modifications to reduce their overall cancer risk, such as avoiding tobacco use, maintaining a healthy body weight, and getting regular exercise.
zic1 gene mutation | Important Points
Conclusion
Mutations in the NBN gene can affect the function of the MRN complex, which is involved in the repair of DNA damage. These mutations can lead to an increased risk of cancer, particularly breast cancer, prostate cancer, and lymphomas/leukemias. In addition, mutations in the NBN gene can cause a rare genetic disorder called Nijmegen breakage syndrome (NBS), which is characterized by growth retardation, microcephaly, immunodeficiency, and an increased susceptibility to cancer.
Testing for NBN gene mutations can be useful for individuals with a family history of NBS or a personal history of cancer. Management of individuals with NBN gene mutations depends on the specific mutation and the individual’s personal and family history of cancer, but generally involves regular surveillance and risk-reducing strategies.