X-linked Severe Combined Immunodeficiency - Genetics

Genetics

X-SCID is caused by a mutation occurring in the xq13.1 locus of the X-chromosome. Most often, this disease affects males whose mother is a carrier (heterozygous) for the disorder. Because females have two X-chromosomes, the mother will not be affected by carrying only one abnormal X-chromosome, but any male children will have a 50% chance of being affected with the disorder by inheriting the faulty gene. Likewise, her female children will have a 50% chance of being carriers for the immunodeficiency. X-SCID can also arise through de novo mutations and X-inactivation. A de novo mutation is an alteration in a gene caused by the result of a mutation in a germ cell (egg or sperm) or in the fertilized egg itself, rather than having been inherited from a carrier. Since only 1/3 of all X-SCID patients have a positive family history of SCID, it is hypothesized that de novo mutations account for a significant percentage of cases. X-inactivation occurs when one of the X-chromosomes on the female becomes inactivated due to a mutation, resulting in the active form of just one chromosome. If their normal X-chromosome has been inactivated, female carriers of X-SCID will have a 100% chance of passing the disorder to their children.