Interleukin-2 receptor γ chain mutation results in X-linked severe combined immunodeficiency in humans

• DOI: 10.1016/0092-8674(93)90167-o
• Publication Date: 2004-05-04T10:14:26Z
• Authors: M Noguchi
• Keywords: Male; 0303 health sciences; X Chromosome; Base Sequence; Genetic Linkage; Molecular Sequence Data; Chromosome Mapping; Receptors, Interleukin-2; Pedigree; 3. Good health; 03 medical and health sciences; Mutation; Humans; Severe Combined Immunodeficiency

The interleukin-2 (IL-2) receptor gamma chain (IL-2R gamma) 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-2R gamma gene to human chromosome Xq13. Genetic linkage analysis indicates that the IL-2R gamma 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-2R gamma 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-2R gamma gene product. Since XSCID is characterized by absent or markedly reduced numbers of T cells, our findings imply that IL-2R gamma 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.