A novel immunodeficiency associated with hypomorphic RAG1 mutations and CMV infection.

[omenn syndrome]

Amorphic mutations in the recombination activating genes RAG 1 and RAG 2 have been reported to cause T - B- SCID , whereas hypomorphic mutations led to the expansion of a few autoimmune T cell clones responsible for the Omenn syndrome phenotype . We report here a novel clinical and immunological phenotype associated with recessive RAG 1 hypomorphic mutations in 4 patients from 4 different families . The immunological phenotype consists of the oligoclonal expansion of TCR gammadelta T cells combined with TCR alphabeta T cell lymphopenia . The clinical phenotype consists of severe , disseminated CMV infection and autoimmune blood cell manifestations . Repertoire studies suggest that CMV infection , in the setting of this particular T cell immunodeficiency , may have driven the TCR gammadelta T cell clonal expansion . This observation extends the range of clinical and immunological phenotypes associated with RAG mutations , emphasizing the role of the genetic background and microbial environment in determining disease phenotype .