RAG mutations in severe combined immunodeficiency and Omenn's syndrome

Recombinase-activating gene (RAG) proteins play a fundamental role in lymphoid development. As heterodimeric endonucleases, they initiate V (D) J recombination, a lymphocyte-specific process that assembles B- and T-cell antigen receptor genes from subgenic V, D, and J elements. Recently, the function 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 immunodeficiency with autoreactive manifestations (i.e., Omenn's syndrome).