Genetics and Severe Combined Immunodeficiency

More than 80 percent of SCID infants do not have a family history of the condition.

Source: NIAID (NIH)1

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Back to: « Severe Combined Immunodeficiency

Back to: « Combined Immunodeficiency

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SCID is caused by defects in different genes involved in the development and function of infection-fighting immune cells. More than a dozen genes have been implicated in SCID, but gene defects are unknown in approximately 15 percent of newborn-screened SCID infants, according to an NIH-funded study.

Source: NIAID (NIH)2

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All forms of SCID are inherited, with as many as half of SCID cases linked to the X chromosome, passed on by the mother.

X-linked SCID results from a mutation in the interleukin 2 receptor gamma (IL2RG) gene which produces the common gamma chain subunit, a component of several IL receptors. IL2RG activates an important signalling molecule, JAK3.

A mutation in JAK3, located on chromosome 19, can also result in SCID. Defective IL receptors and IL receptor pathways prevent the proper development of T-lymphocytes that play a key role in identifying invading agents as well as activating and regulating other cells of the immune system.

In another form of SCID, there is a lack of the enzyme adenosine deaminase (ADA), coded for by a gene on chromosome 20. This means that the substrates for this enzyme accumulate in cells. Immature lymphoid cells of the immune system are particularly sensitive to the toxic effects of these unused substrates, so fail to reach maturity. As a result, the immune system of the afflicted individual is severely compromised or completely lacking.

Source: NCBI, Genes and Disease (NCBI/NIH)3

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Severe combined immunodeficiency (SCID) can be inherited in an X-linked recessive or autosomal recessive manner depending on the genetic cause of the condition. X-linked SCID is the most common type of SCID and is inherited in an X-linked recessive manner.

A condition is X-linked if the changed (mutated) gene responsible for the condition is located on the X chromosome. The X chromosome is one of the two sex chromosomes; females have two X chromosomes and males have one X chromosome and one Y chromosome. In males, one mutated copy of the responsible gene causes signs and symptoms of the condition because they don't have another X chromosome with a working copy of the gene. In females, having one mutated copy of the gene would make them an unaffected carrier; a mutation would have to occur in both copies of the gene to cause the condition. This is why X-linked recessive disorders, including X-linked SCID, occur much more frequently in males. Because fathers only pass their Y chromosome on to their sons, fathers cannot pass X-linked conditions on to their sons.

The other, less common causes of SCID are inherited in an autosomal recessive manner. These types are due to mutations in responsible genes on other chromosomes (not the sex chromosomes). In autosomal recessive conditions, a person must have mutations in both copies of the responsible gene in order to have signs or symptoms of the condition. In most cases, the affected person inherits one mutated copy of the gene from each of the parents, who are typically unaffected carriers. Last updated: 5/27/2014

Source: GARD (NIH)4

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  1. Source: NIAID (NIH): diseases-conditions/ severe-combined-immunodeficiency-scid
  2. Source: NIAID (NIH): diseases-conditions/ scid-causes
  3. Source: NCBI, Genes and Disease (NCBI/NIH): books/ NBK22254/ 
  4. Source: GARD (NIH): diseases/ 7628/ severe-combined-immunodeficiency

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Note: This site is for informational purposes only and is not medical advice. See your doctor or other qualified medical professional for all your medical needs.