Late-Onset Combined Immunodeficiency with a Novel IL2RG Mutation and Probable Revertant Somatic Mosaicism

J Clin Immunol. 2015 Oct;35(7):610-4. doi: 10.1007/s10875-015-0202-0. Epub 2015 Sep 26.


Primary immunodeficiency disease (PID) is caused by mutations of more than two hundred immunity-related genes. In addition to the heterogeneity of the diseases, the atypical presentation of each disease caused by hypomorphic mutations or somatic mosaicism makes genetic diagnosis challenging. Next-generation sequencing tests all genes simultaneously and has proven its innovative efficacy in genomics. We describe a male PID patient without any family history of immunodeficiency. This patient suffered from recurrent infections from 1 year of age. Laboratory analysis showed hypogammaglobulinemia. T, B, and NK cells were present, but the T cell proliferative response decreased. Whole-exome sequencing analysis identified an IL2RG p.P58T missense mutation. CD8(+) and CD56(+) cells showed revertant somatic mosaicism to the wild-type allele. A late-onset and atypical presentation of the X-linked severe combined immunodeficiency (X-SCID) phenotype might be associated with revertant somatic mosaicism in T and NK cells. This patient is the seventh reported case of X-SCID with revertant somatic mosaicism. His classical clinical management did not result in a molecular diagnosis because of the atypical presentation. The coverage that is provided by whole-exome sequencing of most PID genes effectively excluded differential diagnoses other than X-SCID. As next-generation sequencing becomes available in clinical practice, it will enhance our knowledge of PID and rescue currently undiagnosed patients.

Keywords: Combined immunodeficiency; Revertant somatic mosaicism; Whole-exome sequencing; X-linked severe combined immunodeficiency.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aspergillus / immunology*
  • CD8-Positive T-Lymphocytes / physiology*
  • Child
  • Child, Preschool
  • DNA Mutational Analysis / methods
  • Diagnosis, Differential
  • Fatal Outcome
  • Graft Rejection / diagnosis*
  • Graft Rejection / etiology
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Immunologic Deficiency Syndromes / complications
  • Immunologic Deficiency Syndromes / diagnosis*
  • Infant
  • Interleukin Receptor Common gamma Subunit / genetics
  • Interleukin Receptor Common gamma Subunit / metabolism*
  • Invasive Pulmonary Aspergillosis / diagnosis*
  • Invasive Pulmonary Aspergillosis / etiology
  • Japan
  • Male
  • Mosaicism
  • Mutation, Missense / genetics
  • Natural Killer T-Cells / physiology*
  • Pedigree


  • IL2RG protein, human
  • Interleukin Receptor Common gamma Subunit