An immunodeficiency disease with RAG mutations and granulomas.
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.
Schuetz
Catharina
C
Department of Pediatrics and Adolescent Medicine, University Hospital Ulm, Ulm, Germany.
Huck
Kirsten
K
Gudowius
Sonja
S
Megahed
Mosaad
M
Feyen
Oliver
O
Hubner
Bernd
B
Schneider
Dominik T
DT
Manfras
Burkhard
B
Pannicke
Ulrich
U
Willemze
Rein
R
Knüchel
Ruth
R
Göbel
Ulrich
U
Schulz
Ansgar
A
Borkhardt
Arndt
A
Friedrich
Wilhelm
W
Schwarz
Klaus
K
Niehues
Tim
T
D000361:Agammaglobulinemia / Q000235:genetics; D002644:Chickenpox / Q000150:complications; D002648:Child; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000235:genetics*; D005145:Face / Q000473:pathology; D005260:Female; D016654:Genes, RAG-1; D006099:Granuloma / Q000235:genetics* / Q000276:immunology; D006579:Heterozygote; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000150:complications / Q000235:genetics*; D018655:Lymphocyte Count; D016393:Lymphoma, B-Cell / Q000209:etiology; D009154:Mutation; D010375:Pedigree; D012867:Skin / Q000473:pathology; D012871:Skin Diseases / Q000235:genetics* / Q000473:pathology
D004268:DNA-Binding Proteins; C064655:V(D)J recombination activating protein 2