Partial V(D)J recombination activity leads to omenn syndrome

Anna Villa, Sandro Santagata, Fabio Bozzi, Silvia Giliani, Annalisa Frattini, Luisa Imberti, Luisa Benerini Gatta, Hans D. Ochs, Klaus Schwarz, Luigi D. Notarangelo, Paolo Vezzoni, Eugenia Spanopoulou

Research output: Contribution to journalArticlepeer-review


Genomic rearrangement of the antigen receptor loci is initiated by the two lymphoid-specific proteins Rag-1 and Rag-2. Null mutations in either of the two proteins abrogate initiation of V(D)J recombination and cause severe combined immunodeficiency with complete absence of mature B and T lymphocytes. We report here that patients with Omenn syndrome, a severe immunodeficiency characterized by the presence of activated, anergic, oligoclonal T cells, hypereosinophilia, and high IgE levels, bear missense mutations in either the Rag-1 or Rag-2 genes that result in partial activity of the two proteins. Two of the amino acid substitutions map within the Rag- 1 homeodomain and decrease DNA binding activity, while three others lower the efficiency of Rag-1/Rag-2 interaction. These findings provide evidence to indicate that the immunodeficiency manifested in patients with Omenn syndrome arises from mutations that decrease the efficiency of V(D)J recombination.

Original languageEnglish
Pages (from-to)885-896
Number of pages12
Issue number5
Publication statusPublished - May 29 1998

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology


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