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

Cell. 1993 Apr 9;73(1):147-57. doi: 10.1016/0092-8674(93)90167-o.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Sequence
  • Chromosome Mapping
  • Genetic Linkage
  • Humans
  • Male
  • Molecular Sequence Data
  • Mutation
  • Pedigree
  • Receptors, Interleukin-2 / genetics*
  • Severe Combined Immunodeficiency / genetics*
  • X Chromosome


  • Receptors, Interleukin-2