RAG Deficiency
Also written as: RAG — Recombination-Activating Gene
An immunodeficiency caused by mutations in the recombination-activating genes RAG1 or RAG2, impairing V(D)J recombination and resulting in absent or severely reduced T- and B-lymphocytes.
Full Definition
Recombination-activating gene (RAG) deficiency encompasses a spectrum of conditions caused by biallelic loss-of-function or hypomorphic mutations in RAG1 or RAG2. These genes encode proteins essential for V(D)J recombination, the somatic DNA rearrangement process that generates diverse antigen receptor repertoires on T and B cells. Complete RAG deficiency presents as classic T-B-NK+ SCID, while hypomorphic mutations produce attenuated phenotypes including Omenn syndrome, combined immunodeficiency with granulomas, or late-onset antibody deficiency. Editors must correctly expand the acronym RAG as 'recombination-activating gene' (not 'recombination activation gene') and note that the genes are always italicised (RAG1, RAG2) when referring to the gene loci, but roman when referring to the protein products.
Usage
Usage note: Gene symbols RAG1 and RAG2 must be italicised in manuscripts following HGNC convention. 'RAG deficiency' (roman) refers to the clinical condition. Do not write 'RAG activation gene'.
In Context
- "Whole-exome sequencing revealed biallelic RAG1 mutations, confirming RAG deficiency as the underlying cause of the infant's T-B-NK+ SCID phenotype." — Genetic diagnostic report
- "The review article failed to italicise RAG1 when referring to the gene locus; the copy-editor corrected all instances to conform to HGNC nomenclature." — Manuscript copy-edit annotation