Immune consequences of mutations in the human common gamma-chain gene

Mol Genet Metab. 2002 Jul;76(3):163-71. doi: 10.1016/s1096-7192(02)00042-2.


A mutation (c.878T>A) in the common gamma chain (gamma(c)) causes an X-linked combined immunodeficiency (XCID) in a large kindred of British origin. In the disease, gamma(c) is expressed, but its binding to Jak3 is reduced. The immune deficiencies and clinical course were less marked in toddlers and school age children with XCID(L293Q) than in severe combined immunodeficiency (SCID). However, affected newborns were profoundly deficient in thymic size and T cells. In some affected infants, thymic size and numbers of T cells gradually increased during the first year. Their clinical course was relatively benign. In affected infants of one lineage, the number of blood T cells failed to increase substantially. They succumbed to opportunistic infections. T cell deficiencies in XCID(L293Q) progressively worsened during adolescence. Decreased thymic function, failure to rescue T cells from apoptosis, and replication senescence were possible causes. Blood T cells with the phenotype CD45RA(+)CD62L(+) (unstimulated T cells) were most depressed. CD4(+) T cells were also deficient in a specific marker of recent thymic emigrants, episomal DNA deletion circles created during TcR gene rearrangements. Apoptosis of T cells was increased, but neither apoptosis nor cell death was age-related. In contrast, telomere shortening in T cells increased with age. Unlike murine gamma(c) gene deletions, gamma delta T cells were prominent in affected adolescents and young adults. Furthermore, T cells with a V delta 2/V gamma 9 specificity declined with age and were replaced in the oldest male with a V delta 1 specificity. Thus, the mutation provides many insights concerning the role of gamma(c) in the biology of T cells.

Publication types

  • Review

MeSH terms

  • Chromosomes, Human, X
  • Female
  • Genetic Linkage
  • Humans
  • Immunologic Deficiency Syndromes / genetics*
  • Immunologic Deficiency Syndromes / immunology
  • Immunophenotyping
  • Infant
  • Interleukin Receptor Common gamma Subunit
  • Male
  • Mutation*
  • Pedigree
  • Receptors, Interleukin-7 / genetics*


  • IL2RG protein, human
  • Interleukin Receptor Common gamma Subunit
  • Receptors, Interleukin-7