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Two mutational hotspots in the interleukin-2 receptor gamma chain gene causing human X-linked severe combined immunodeficiency.

Publication ,  Journal Article
Pepper, AE; Buckley, RH; Small, TN; Puck, JM
Published in: Am J Hum Genet
September 1995

Human severe combined immunodeficiency (SCID), a syndrome of profoundly impaired cellular and humoral immunity, is most commonly caused by mutations in the X-linked gene for interleukin-2 (IL-2) receptor gamma chain (IL2RG). For mutational analysis of IL2RG in males with SCID, SSCP screening was followed by DNA sequencing. Of 40 IL2RG mutations found in unrelated SCID patients, 6 were point mutations at the CpG dinucleotide at cDNA 690-691, encoding amino acid R226. This residue lies in the extracellular domain of the protein in a region not previously recognized to be significantly conserved in the cytokine receptor gene family, 11 amino acids upstream from the highly conserved WSXWS motif. Three additional instances of mutation at another CpG dinucleotide at cDNA 879 produced a premature termination signal in the intracellular domain of IL2RG, resulting in loss of the SH2-homologous intracellular domain known to be essential for signaling from the IL-2 receptor complex. Mutations at these two hotspots constitute > 20% of the X-linked SCID mutations found by our group and a similar proportion of all reported IL2RG mutations.

Duke Scholars

Published In

Am J Hum Genet

ISSN

0002-9297

Publication Date

September 1995

Volume

57

Issue

3

Start / End Page

564 / 571

Location

United States

Related Subject Headings

  • X Chromosome
  • Severe Combined Immunodeficiency
  • Receptors, Interleukin-2
  • Polymorphism, Single-Stranded Conformational
  • Polymerase Chain Reaction
  • Phenotype
  • Mutation
  • Molecular Sequence Data
  • Male
  • Humans
 

Citation

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Chicago
ICMJE
MLA
NLM
Pepper, A. E., Buckley, R. H., Small, T. N., & Puck, J. M. (1995). Two mutational hotspots in the interleukin-2 receptor gamma chain gene causing human X-linked severe combined immunodeficiency. Am J Hum Genet, 57(3), 564–571.
Pepper, A. E., R. H. Buckley, T. N. Small, and J. M. Puck. “Two mutational hotspots in the interleukin-2 receptor gamma chain gene causing human X-linked severe combined immunodeficiency.Am J Hum Genet 57, no. 3 (September 1995): 564–71.
Pepper, A. E., et al. “Two mutational hotspots in the interleukin-2 receptor gamma chain gene causing human X-linked severe combined immunodeficiency.Am J Hum Genet, vol. 57, no. 3, Sept. 1995, pp. 564–71.
Journal cover image

Published In

Am J Hum Genet

ISSN

0002-9297

Publication Date

September 1995

Volume

57

Issue

3

Start / End Page

564 / 571

Location

United States

Related Subject Headings

  • X Chromosome
  • Severe Combined Immunodeficiency
  • Receptors, Interleukin-2
  • Polymorphism, Single-Stranded Conformational
  • Polymerase Chain Reaction
  • Phenotype
  • Mutation
  • Molecular Sequence Data
  • Male
  • Humans