An immunodeficiency disease with RAG mutations and granulomas

N Engl J Med. 2008 May 8;358(19):2030-8. doi: 10.1056/NEJMoa073966.


We describe three unrelated girls who had an immunodeficiency disease with granulomas in the skin, mucous membranes, and internal organs. All three girls had severe complications after viral infections, including B-cell lymphoma associated with Epstein-Barr virus (EBV). Other findings were hypogammaglobulinemia, a diminished number of T and B cells, and sparse thymic tissue on ultrasonography. Molecular analysis revealed that the patients were compound heterozygotes for mutations in recombination activating gene 1 or 2 (RAG1 or RAG2). In each case, both parents were heterozygous carriers of a RAG mutation. The mutations were associated with reduced function of RAG in vitro (3 to 30% of normal activity). The parents and one sibling in the three families were healthy.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agammaglobulinemia / genetics
  • Chickenpox / complications
  • Child
  • Child, Preschool
  • DNA-Binding Proteins / genetics*
  • Face / pathology
  • Female
  • Genes, RAG-1*
  • Granuloma / genetics*
  • Granuloma / immunology
  • Heterozygote
  • Humans
  • Immunologic Deficiency Syndromes / complications
  • Immunologic Deficiency Syndromes / genetics*
  • Lymphocyte Count
  • Lymphoma, B-Cell / etiology
  • Mutation*
  • Pedigree
  • Skin / pathology
  • Skin Diseases / genetics*
  • Skin Diseases / pathology


  • DNA-Binding Proteins
  • V(D)J recombination activating protein 2