Tirosh I, et al. - Researchers measured the recombinase activity of naturally occurring Recombinase Activating Gene 2 (RAG2) mutant proteins by using a flow cytometry-based assay and correlated the results with the severity of the clinical and immunological phenotype. They found a wide range of recombination activity was shown by RAG2 variants. Significantly lower activity was reported for mutations associated with severe combined immune deficiency (SCID) and Omenn syndrome, compared with those detected in patients with less severe clinical presentations. Four variants (P253R, F386L, N474S, and M502V) had wild-type levels of activity. With the use of bicistronic vectors, it was possible to evaluate more carefully the impact of compound heterozygous mutations, with good correlation between Green Fluorescent Protein expression and number and diversity of immunoglobulin heavy chain rearrangements.