People with LIG4 syndrome are unable to effectively repair damage to the DNA of their cells. (Image credit: CHRISTOPH BURGSTEDT/SCIENCE PHOTO LIBRARY via Getty Images)
Disease name: DNA ligase IV syndrome (LIG4)
Affected groups: LIG4 syndrome is an extremely rare inherited disorder first reported in the UK in 1990. Little is known about its exact prevalence worldwide, but as of 2020, approximately 55 cases have been documented in the medical literature.
Causes: LIG4 syndrome is caused by a mutation in the LIG4 gene, which contains instructions for making a protein known as DNA ligase 4. This protein is an enzyme that helps repair a certain type of DNA damage, namely breaks on either side of the DNA double helix.
Such breaks occur quite frequently, between 10 and 50 times a day in a typical human cell. These breaks can be caused by a variety of factors, including normal cellular processes such as DNA replication, which is necessary for cell division, as well as external influences such as exposure to certain chemicals or radiation.
If these breaks in DNA are not repaired, they can cause cells to self-destruct or, alternatively, become cancerous. Because LIG4 syndrome disrupts this process, people with the condition are particularly vulnerable to the negative effects of radiation.
The enzyme DNA ligase 4 is also needed to synthesize vital proteins on the surface of immune cells, such as T cells and B cells, which help them function properly and produce antibodies to fight infections. Therefore, people with LIG4 may develop an immunodeficiency disorder similar to severe combined immunodeficiency due to their condition.
LIG4 syndrome is inherited in an autosomal recessive manner, meaning that for the disorder to occur, a child must inherit two copies of the defective LIG4 gene—one from each parent.
12 year old child with LIG4 syndrome.
Symptoms: People with LIG4 syndrome typically experience a range of symptoms that may appear either soon after birth or later in life. These symptoms include microcephaly, in which the baby's brain is significantly smaller than expected, delays in growth and development, and a decrease in the number of cells in the blood, including immune cells that help the body fight infections.
Other characteristic features of LIG4 syndrome include a bird-like facial appearance and skin lesions. Patients may also have abnormal skeletal shape and progressive bone marrow failure; bone marrow is the main
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