title: Missense mutation in exon 7 of the common gamma chain gene causes a moderate form of X-linked combined immunodeficiency.
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 gamma chain (gamma 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), 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 gamma c gene in this pedigree. A missense mutation in the region coding for the cytoplasmic portion of the gamma c gene was found in three affected males but not in a normal brother. Therefore, this point mutation in the gamma c gene leads to a less severe degree of deficiency in cellular and humoral immunity than that seen in XSCID.
authors.affiliation: Department of Pediatrics, University of Texas Medical Branch, Galveston 77555-0369.
authors.forename: F C
authors.initials: FC
authors.lastname: Schmalstieg
authors.forename: W J
authors.initials: WJ
authors.lastname: Leonard
authors.forename: M
authors.initials: M
authors.lastname: Noguchi
authors.forename: M
authors.initials: M
authors.lastname: Berg
authors.forename: H E
authors.initials: HE
authors.lastname: Rudloff
authors.forename: R M
authors.initials: RM
authors.lastname: Denney
authors.forename: S K
authors.initials: SK
authors.lastname: Dave
authors.forename: E G
authors.initials: EG
authors.lastname: Brooks
authors.forename: A S
authors.initials: AS
authors.lastname: Goldman
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002877:Chromosomes, Human / Q000235:genetics*; D004303:Dosage Compensation, Genetic; D005091:Exons / Q000235:genetics; D005260:Female; D008040:Genetic Linkage / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000209:etiology / Q000235:genetics*; D008214:Lymphocytes / Q000166:cytology; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010375:Pedigree; D011110:Polymorphism, Genetic; D011944:Receptors, Androgen / Q000235:genetics*; D014960:X Chromosome / Q000235:genetics*
chemical_list: D011944:Receptors, Androgen