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Partial V(D)J recombination activity leads to Omenn syndrome.

Authors: Villa, A  Santagata, S  Bozzi, F  Giliani, S  Frattini, A  Imberti, L  Gatta, LB  Ochs, HD  Schwarz, K  Notarangelo, LD  Vezzoni, P  Spanopoulou, E 
Citation: Villa A, etal., Cell. 1998 May 29;93(5):885-96.
Pubmed: (View Article at PubMed) PMID:9630231

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.


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RGD Object Information
RGD ID: 1599403
Created: 2007-02-01
Species: All species
Last Modified: 2007-02-01
Status: ACTIVE


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