RAG mutations in severe combined immunodeficiency and Omenn's syndrome

Recombinase-activating gene (RAG) proteins play a fundamental role in lymph oid development. As heterodimeric endonucleases, they initiate V (D) J reco mbination, a lymphocyte-specific process that assembles B- and T-cell antig en receptor genes from subgenic V, D, and J elements. Recently, the functio n of the RAG protein domains has been characterized better. A complete loss of RAG function causes SCID without B and T cells (B-T- SCID). Hypomorphic RAG alleles with residual V (D) J recombination function result in an immu nodeficiency with autoreactive manifestations (i.e., Omenn's syndrome).