RGD Reference Report - Partial V(D)J recombination activity leads to Omenn syndrome. - Rat Genome Database

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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.
RGD ID: 1599403
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.


Disease Annotations    

Objects Annotated

Genes (Rattus norvegicus)
Rag1  (recombination activating 1)
Rag2  (recombination activating 2)

Genes (Mus musculus)
Rag1  (recombination activating 1)
Rag2  (recombination activating gene 2)

Genes (Homo sapiens)
RAG1  (recombination activating 1)
RAG2  (recombination activating 2)

Additional Information