INTERLEUKIN-2 RECEPTOR GAMMA CHAIN MUTATION RESULTS IN X-LINKED SEVERE COMBINED IMMUNODEFICIENCY IN HUMANS

The interleukin-2 (IL-2) receptor gamma chain (IL-2Rgamma) is a component of high and intermediate affinity IL-2 receptors that is required to achieve full ligand binding affinity and internalization. We have localized the IL-2Rgamma gene to human chromosome Xq13. Genetic linkage analysis indicates that the IL-2Rgamma gene and the locus for X-linked severe combined immunodeficiency (XSCID) appear to be at the same position. Moreover, we demonstrate that each of three unrelated patients with XSCID has a different mutation in his IL-2Rgamma gene resulting in a different premature stop codon and predicted C-terminal truncation. These data establish that XSCID is associated with mutations of the IL-2Rgamma gene product. Since XSCID is characterized by absent or markedly reduced numbers of T cells, our findings imply that IL-2Rgamma plays a vital role in thymic maturation of T cells. These results also have important implications for prenatal and postnatal diagnosis, carrier female detection, and gene therapy for XSCID.