title: Omenn syndrome does not live by V(D)J recombination alone.
abstract: OBJECTIVE
  During the past decade, easy access to sequence analyses has allowed us to increase our understanding of the pathogenesis of severe combined immunodeficiencies. Here, we describe the expanding clinical and immunological spectrum associated with Omenn syndrome phenotype. In particular, we review the cellular and molecular mechanisms involved in the pathophysiology of 'classical' Omenn syndrome due to the recombination activating gene (RAG) defects and of a new subgroup of Omenn-like disorders.
  
  
  RESULTS
  Different types of mutations are associated with the Omenn phenotype characterized by skin erythroderma, oligoclonal-activated T cells and elevated IgE in the absence of circulating B cells. Extensive studies conducted over the last few years have allowed the definition of the 'classical form' of Omenn syndrome due to hypomorphic defects in genes involved in V(D)J recombination, mainly RAG genes, and 'Omenn-like' features associated with mutations in genes involved in the maturation steps of lymphoid cells other than V(D)J recombination. Moreover, an increasing number of diseases other than those due to V(D)J recombination defects develop Omenn signs.
  
  
  CONCLUSIONS
  Impaired but not abolished V(D)J recombination process leads to the generation of a few T cells which expand in the periphery, infiltrate target organs such as skin and gut, resulting in severe erythroderma and colitis, both typical signs of Omenn syndrome. Extensive molecular studies now demonstrate that genes other than V(D)J molecules have a role in the pathogenesis of this disease, supporting the evidence that 'Omenn' defines an inflammatory condition associated with various genetic defects.
authors: Institute of Genetic and Biomedical Research, Milan Unit, National Research Council (CNR), Milan bIstituto Clinico Humanitas IRCCS, Rozzano, Italy.
authors: Veronica
authors: V
authors: Marrella
authors: Virginia
authors: V
authors: Maina
authors: Anna
authors: A
authors: Villa
mesh_terms: D000243:Adenosine Deaminase / Q000235:genetics; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D015851:Interleukin-7 / Q000235:genetics; D008213:Lymphocyte Activation; D009154:Mutation / Q000235:genetics; D016511:Severe Combined Immunodeficiency / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D060152:V(D)J Recombination / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D015851:Interleukin-7; C064655:V(D)J recombination activating protein 2; C064658:RAG-1 protein; D000243:Adenosine Deaminase