title: RAG-dependent primary immunodeficiencies.
abstract: Mutations in recombination activating genes 1 and 2 (RAG1 and RAG2) cause a spectrum of severe immunodeficiencies ranging from classical T cell-B cell-severe combined immunodeficiency (T(-)B(-)SCID) and Omenn syndrome (OS) to an increasing number of peculiar cases. While it is well established from biochemical data that the specific genetic defect in either of the RAG genes is the first determinant of the clinical presentation, there is also increasing evidence that environmental factors play an important role and can lead to a different phenotypic expression of a given genotype. However, a better understanding of the mechanisms by which the molecular defect impinges on the cellular phenotype of OS is still lacking. Ongoing studies in knock-in mice could better clarify this aspect.
authors.affiliation: Istituto di Tecnologie Biomediche, Segrate, Milan, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Sobacchi
authors.forename: Veronica
authors.initials: V
authors.lastname: Marrella
authors.forename: Francesca
authors.initials: F
authors.lastname: Rucci
authors.forename: Paolo
authors.initials: P
authors.lastname: Vezzoni
authors.forename: Anna
authors.initials: A
authors.lastname: Villa
mesh_terms: D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016654:Genes, RAG-1 / Q000502:physiology*; D018398:Homeodomain Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics*; D008954:Models, Biological; D009154:Mutation; D011995:Recombination, Genetic; D045567:VDJ Recombinases / Q000502:physiology
chemical_list: D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C064655:V(D)J recombination activating protein 2; C064658:RAG-1 protein; D045567:VDJ Recombinases