X-linked severe combined immunodeficiency
- X-linked SCID
- Severe combined immunodeficiency, X-linked
- SCID, X-linked
- Severe combined immunodeficiency T- B+ due to gamma chain deficiency
- Severe combined immunodeficiency, X-linked, T cell-negative, B cell-positive, NK cell-negative
Your QuestionIn the case of X-linked SCID, if a girl has SCID it means she inherited a defective X gene from both parents. But if the father has a defective X gene, he would have to be affected with SCID. How can a father just be a carrier in the case of an affected daughter? And what is the risk in a subsequent pregnancy to have SCID if both parents are carriers? Is it possible for a male to be a carrier?
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Questions on this page
- How is X-linked severe combined immunodeficiency inherited?
- Can a male be an unaffected carrier of X-linked severe combined immunodeficiency?
- Can a female have X-linked severe combined immunodeficiency?
- What is the risk to have a child with severe combined immunodeficiency if both parents are carriers?
- How can I find a genetics professional in my area?
The father of a boy with X-SCID cannot have the disease and cannot be a carrier (having a mutated copy of the responsible gene would make him affected). If an affected boy is the only affected family member, either his mother is a carrier or the mutation occurred for the first time in the affected boy (a de novo mutation). It is thought that about 2/3 of these cases are inherited from a carrier mother, and about 1/3 are due to new de novo mutations.
If there is more than one affected family member, it is assumed that the mother of the affected boy is a carrier. A carrier mother has a 50% risk to pass on the mutation in each pregnancy. Males who inherit the mutation will be affected, and females who inherit the mutation will be unaffected carriers. A man with X-SCID will pass the mutation to all of his daughters and none of his sons.
Genetic testing can often determine which family member had the first mutation. Identifying this family member is important for learning which branches of a family are at risk for X-SCID. Carrier testing for at-risk relatives and prenatal testing for pregnancies at increased risk are possible if the disease-causing IL2RG mutation has been identified in the family.
People with a family history of X-SCID who are interested in learning about genetic risks to themselves and family members should speak with a genetics professional.
There is a condition related to X-SCID called 'atypical X-SCID,' in which a mutation in the same disease-causing gene results in production of a small amount of the gene product, or a protein with residual activity (i.e. the mutation is less severe). Males with this type of mutation may have an unregulated immune response and autoimmunity associated with rashes, gastrointestinal malabsorption, an enlarged spleen, and short stature.
You can learn more about the different types of SCID and their inheritance patterns on the Immune Deficiency Foundation's Web site.
- she inherits a disease-causing mutation on one X chromosome from a carrier mother, and has a new (de novo) mutation on the gene on the other X chromosome (since it is not possible for her father to be an unaffected carrier)
- she inherits one mutation from a carrier mother, and another from an affected father
- she has two de novo mutations
Again, we are not aware of any reports of affected females. The presence of non-X-linked forms of SCID (autosomal recessive forms) should be considered for female infants who have signs and symptoms of SCID, and for any infant who has physical features of a syndrome associated with the types of immunodeficiencies seen in SCID. Examples may include 22q11.2 deletion syndrome and CHARGE syndrome.
If both parents are carriers of the same autosomal recessive form of SCID, each child would have a 25% (1 in 4) risk to be affected, a 50% (1 in 2) risk to be an unaffected carrier like each parent, and a 25% risk to be affected. These risks apply to both male and female offspring.
If the mother is a carrier of X-linked SCID and the father is a carrier of an autosomal recessive form of SCID, there is only a risk of X-linked SCID in their male children. The mother has a 50% risk to pass on the disease-causing mutation in each pregnancy. All males who inherit the mutation will be affected, and all females who inherit the mutation will be carriers.
Because it is not possible for a male to be an unaffected carrier of X-linked SCID, parents cannot both be carriers of this type.
- Eric Allenspach, David J Rawlings, and Andrew M Scharenberg. X-Linked Severe Combined Immunodeficiency. GeneReviews. January 24, 2013; http://www.ncbi.nlm.nih.gov/books/NBK1410/. Accessed 5/28/2014.