XLP can be caused by variations in the genetic makeup of a person. Genes are part of our genetic makeup and provide the instructions our cells need to perform their different roles within our bodies. XLP can be caused by changes or mutations in either of two genes: SH2D1A or XIAP / BIRC4. When these genes are defective, the immune system doesn’t function correctly, and the manifestations of XLP develop.
How is XLP inherited?
XLP1 and XLP2 are both X-linked diseases, which mean the genes which cause them are located on the X chromosome. Boys have one X chromosome and one Y chromosome. Girls have two X chromosomes. When a boy has an X chromosome that has a mutated, or “bad,” copy of the SH2D1A or XIAP / BIRC4 gene, he develops XLP.
Mothers or sisters of patients with XLP may also have an X chromosome that has a bad copy of the SH2D1A or XIAP / BIRC4 gene. Since females have two X chromosomes, most females will never have any symptoms of the disease because there is a normal copy of the gene on their other X chromosome. Very rarely, female carriers may also develop symptoms of XLP1.
In most cases, affected patients inherit the X chromosome with the bad copy of the gene from their mother. In some cases, the mutation spontaneously occurs in the child.
I am an XLP carrier. What are the chances my children are affected?
Women who have a bad copy of an XLP gene on one of their X chromosomes are called carriers. For these women, every pregnancy has a 50 percent chance of receiving the X chromosome with the bad copy of the gene. Every male child of an XLP carrier has a 50 percent chance of being affected by XLP. Every female child has a 50 percent chance of being a carrier, but will probably never be sick, though her future male children may be affected.