title: Interleukin-2 receptor gamma chain mutation results in X-linked severe combined immunodeficiency in humans.
abstract: 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.
authors: Section on Pulmonary and Molecular Immunology, National Heart, Lung, and Blood Institute, Bethesda, Maryland 20892.
authors: M
authors: M
authors: Noguchi
authors: H
authors: H
authors: Yi
authors: H M
authors: HM
authors: Rosenblatt
authors: A H
authors: AH
authors: Filipovich
authors: S
authors: S
authors: Adelstein
authors: W S
authors: WS
authors: Modi
authors: O W
authors: OW
authors: McBride
authors: W J
authors: WJ
authors: Leonard
mesh_terms: D001483:Base Sequence; D002874:Chromosome Mapping; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D015375:Receptors, Interleukin-2 / Q000235:genetics*; D016511:Severe Combined Immunodeficiency / Q000235:genetics*; D014960:X Chromosome
chemical_list: D015375:Receptors, Interleukin-2