Recent advances in understanding RAG deficiencies [version 1; referees: 2 approved]

• Main Author: Andrew Gennery
• Format: Article
• Language: English
• Published: F1000 Research Ltd 2019-02-01
• Series: F1000Research
• Online Access: https://f1000research.com/articles/8-148/v1

Recombination-activating genes (RAG)1 and RAG2 initiate the molecular processes that lead to lymphocyte receptor formation through VDJ recombination. Nonsense mutations in RAG1/RAG2 cause the most profound immunodeficiency syndrome, severe combined immunodeficiency (SCID). Other severe and less-severe clinical phenotypes due to mutations in RAG genes are now recognized. The degree of residual protein function may permit some lymphocyte receptor formation, which confers a less-severe clinical phenotype. Many of the non-SCID phenotypes are associated with autoimmunity. New findings into the effect of mutations in RAG1/2 on the developing T- and B-lymphocyte receptor give insight into the development of autoimmunity. This article summarizes recent findings and places the genetic and molecular findings in a clinical context.