Relative CD4 lymphopenia and a skewed memory phenotype are the main immunologic abnormalities in a child with Omenn syndrome due to homozygous RAG1-C2633T hypomorphic mutation

Clin Immunol. 2009 Jun;131(3):447-55. doi: 10.1016/j.clim.2009.01.014. Epub 2009 Feb 25.


We report a child with Omenn syndrome (OS) due to homozygous RAG1-C2633T mutations who had an unusual clinical and immunological presentation. She had delayed onset of OS-associated clinical features, had cleared a number of potentially fatal pathogens including respiratory syncytial virus, parainfluenza-3 virus and rotavirus, and was thriving at diagnosis. Laboratory assessment showed normal T and B lymphocyte number and function. T-cell-receptor repertoire in the blood was relatively diverse and her primary immunologic abnormality was skewing of circulating T-cells to the memory phenotype. A compelling explanation for the perplexing combination in OS of atopic/autoimmune and immunologic features has proven elusive. Homozygous RAG1-C2633T hypomorphic mutation may lead to significant residual immunity and a skewed memory phenotype. Our findings suggest that, in addition to host-genetic factors, environment, and/or pathogens, hypomorphic RAG mutations may differentially impact on V(D)J recombination activity and hence lead to a variable ability to sustain T and B cell lymphopoiesis. Importantly, this case emphasizes that such hypomorphic mutations may promote an attenuated phenotype, complicating the diagnosis of primary immunodeficiency (PID).

Publication types

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

MeSH terms

  • CD4-Positive T-Lymphocytes / immunology*
  • Child
  • Female
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / immunology
  • Humans
  • Lymph Nodes / pathology
  • Lymphopenia / etiology
  • Lymphopenia / genetics
  • Lymphopenia / immunology*
  • Mutation / genetics
  • Severe Combined Immunodeficiency / complications
  • Severe Combined Immunodeficiency / genetics
  • Severe Combined Immunodeficiency / immunology*
  • Skin / pathology
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism


  • Homeodomain Proteins
  • RAG-1 protein