title: Efficient detection of thirty-seven new IL2RG mutations in human X-linked severe combined immunodeficiency.
abstract: X-linked severe combined immunodeficiency (XSCID) is a rare and potentially fatal disease caused by mutations of IL2RG, the gene encoding the interleukin-2 receptor gamma chain, a component of multiple cytokine receptors that are essential for lymphocyte development and function. To date, over 100 different mutations of IL2RG resulting in XSCID have been published. Using nonradioactive, direct DNA sequencing of a single PCR amplicon containing the whole IL2RG gene, we found IL2RG mutations in 78 previously unpublished unrelated cases of XSCID. We report 37 newly identified mutations of IL2RG, including 23 point mutations, 10 small deletions, 3 instances of the same single nucleotide insertion, 1 large deletion, and 2 complex mutations. More than half of the mutations (22 of 37) were predicted to result in unstable IL2RG mRNA. The remaining 14 mutations disrupted conserved functional motifs common to all cytokine receptor family members; changed protein conformation, charge, or hydrophobicity; or altered the intracellular portion of the protein, which is critical for proper interaction with signal-transducing molecules including Janus family tyrosine kinase 3.
authors.affiliation: Section of Molecular Diagnostics, Clinical Pathology Department, Clinical Center, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Niemela
authors.forename: J M
authors.initials: JM
authors.lastname: Puck
authors.forename: R E
authors.initials: RE
authors.lastname: Fischer
authors.forename: T A
authors.initials: TA
authors.lastname: Fleisher
authors.forename: A P
authors.initials: AP
authors.lastname: Hsu
mesh_terms: D001483:Base Sequence; D008040:Genetic Linkage; D006801:Humans; D018655:Lymphocyte Count; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D015375:Receptors, Interleukin-2 / Q000235:genetics*; D017422:Sequence Analysis, DNA / Q000379:methods; D016511:Severe Combined Immunodeficiency / Q000235:genetics*; D014960:X Chromosome
chemical_list: D015375:Receptors, Interleukin-2