More than just SCID--the phenotypic range of combined immunodeficiencies associated with mutations in the recombinase activating genes (RAG) 1 and 2.

[omenn syndrome]

Combined immunodeficiencies with impaired numbers and function of T - and B-cells can be attributed to defects in the recombinase activating genes (RAG ). The products of these genes , the RAG 1 and 2 proteins , are key players in the V (D )J recombination process leading to the assembly of antigen receptor genes . Complete RAG deficiency (RAGD ) with no V (D )J (<1 % recombination activity of wild type ) is associated with classical SCID and absence of T - and B-cells . In RAGD with residual V (D )J activity (>1 % recombination activity of wild type ), several clinical and immunological subtypes have been described : RAGD with skin inflammation and alphabeta T -cell expansion (classical Omenn syndrome ), RAGD with skin inflammation and without T -cell expansion (incomplete Omenn syndrome ), RAGD with gammadelta T -cell expansion and RAGD with granulomas . Engraftment of maternal T -cells can add to variation in phenotype . The potential role of epigenetic factors that influence the emergence of these phenotypes is discussed . Thorough assessment and interpretation of clinical and immunological findings will guide treatment modalities as intense as hematopoietic stem cell transplantation .