Missense mutation in exon 7 of the common γ chain gene causes a moderate form of X-linked combined immunodeficiency

Frank C. Schmalstieg, Warren J. Leonard, Masayuki Noguchi, Maria Berg, H. Elizabeth Rudloff, Richard M. Denney, Sanat K. Dave, Edward G. Brooks, Armond S. Goldman

Research output: Contribution to journalArticle

72 Scopus citations

Abstract

Clinical and immunologic features of a recently recognized X-linked combined immunodeficiency disease (XCID) suggested that XCID and X-linked severe combined immunodeficiency (XSCID) might arise from different genetic defects. The recent discovery of mutations in the common γ chain (γ(c)) gene, a constituent of several cytokine receptors, in XSCID provided an opportunity to test directly whether a previously unrecognized mutation in this same gene was responsible for XCID. The status of X chromosome inactivation in blood leukocytes from obligate carriers of XCID was determined from the polymorphic, short tandem repeats (CAG)(n) in the androgen receptor gene, which also contains a methylation-sensitive HpaII site. As in XSCID, X-chromosome inactivation in obligate carriers of XCID was nonrandom in T and B lymphocytes. In addition, X chromosome inactivation in PMNs was variable. Findings from this analysis prompted sequencing of the γ(c) gene in this pedigree. A missense mutation in the region coding for the cytoplasmic portion of the γ(c) gene was found in three affected males but not in a normal brother. Therefore, this point mutation in the γ(c) gene leads to a less severe degree of deficiency in cellular and humoral immunity than that seen in XSCID.

Original languageEnglish (US)
Pages (from-to)1169-1173
Number of pages5
JournalJournal of Clinical Investigation
Volume95
Issue number3
DOIs
StatePublished - Mar 1995
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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    Schmalstieg, F. C., Leonard, W. J., Noguchi, M., Berg, M., Rudloff, H. E., Denney, R. M., Dave, S. K., Brooks, E. G., & Goldman, A. S. (1995). Missense mutation in exon 7 of the common γ chain gene causes a moderate form of X-linked combined immunodeficiency. Journal of Clinical Investigation, 95(3), 1169-1173. https://doi.org/10.1172/JCI117765