title: Mutation analysis of IL2RG in human X-linked severe combined immunodeficiency.
abstract: Severe combined immunodeficiency (SCID) is a syndrome of profoundly impaired cellular and humoral immunity. In humans, SCID is most commonly caused by mutations in the X-linked gene IL2RG, which encodes the common gamma chain, gamma c, of the leukocyte receptors for interleukin-2 and multiple other cytokines. To investigate the frequency and variety of IL2RG mutations that cause SCID, we analyzed DNA, RNA, and B-cell lines from a total of 103 unrelated SCID-affected males and their relatives using a combination of molecular and immunologic techniques. Sixty-two different mutations spanning all eight IL2RG exons were found in 87 cases, making possible correlations between mutation type and functional consequences. Although skewed maternal X chromosome inactivation, single-strand conformation polymorphism, mRNA expression, and cell surface staining with anti-gamma c antibodies were all helpful in establishing IL2RG defects as the cause of SCID, only dideoxy fingerprinting and DNA sequence determination each detected 100% of the IL2RG mutations in our series. Abnormal gamma c chains may be expressed in the lymphocytes of as many as two thirds of patients with X-linked SCID. Specific mutation diagnosis thus remains technically challenging, but it is important for genetic counseling and perhaps for helping to select appropriate subjects for retroviral gene therapy trials, This is a US government work. There are no restrictions on its use.
authors.affiliation: Laboratory for Gene Transfer, National Center for Human Genome Research, Bethesda, MD 20892-4442, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Puck
authors.forename: A E
authors.initials: AE
authors.lastname: Pepper
authors.forename: P S
authors.initials: PS
authors.lastname: Henthorn
authors.forename: F
authors.initials: F
authors.lastname: Candotti
authors.forename: J
authors.initials: J
authors.lastname: Isakov
authors.forename: T
authors.initials: T
authors.lastname: Whitwam
authors.forename: M E
authors.initials: ME
authors.lastname: Conley
authors.forename: R E
authors.initials: RE
authors.lastname: Fischer
authors.forename: H M
authors.initials: HM
authors.lastname: Rosenblatt
authors.forename: T N
authors.initials: TN
authors.lastname: Small
authors.forename: R H
authors.initials: RH
authors.lastname: Buckley
mesh_terms: D016172:DNA Fingerprinting; D004252:DNA Mutational Analysis; D004251:DNA Transposable Elements; D017353:Gene Deletion; D005787:Gene Frequency; D008040:Genetic Linkage; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D008297:Male; D017354:Point Mutation; D018807:Polymorphism, Single-Stranded Conformational; D011485:Protein Binding; D012326:RNA Splicing; D012333:RNA, Messenger / Q000096:biosynthesis; D018121:Receptors, Cytokine / Q000096:biosynthesis; D015375:Receptors, Interleukin-2 / Q000235:genetics* / Q000378:metabolism; D012680:Sensitivity and Specificity; D016511:Severe Combined Immunodeficiency / Q000235:genetics*; D014960:X Chromosome
chemical_list: D004251:DNA Transposable Elements; D007376:Interleukin-2; D012333:RNA, Messenger; D018121:Receptors, Cytokine; D015375:Receptors, Interleukin-2