An immunodeficiency disease with RAG mutations and granulomas

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

Abstract

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

Substances

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