title: Recombinase-activating gene 1 immunodeficiency: different immunological phenotypes in three siblings.
abstract: We report different immunological phenotypes in three siblings from consanguineous family with recombinase-activating gene 1 (RAG1) gene mutations. Null mutations of RAG genes result in severe combined immunodeficiency (SCID) with absent T and B cells. Hypomorphic mutations with retained activity of RAG genes may lead to a 'leaky' SCID with some features of Omenn syndrome (OS) or typical OS. In our three patients, homozygous, hypomorphic RAG1 gene mutation (g.368-369delAA) was detected. Two patients presented with T-B-SCID phenotype while the youngest patient developed T+B+NK+SCID phenotype with expansion of autologous T-cell receptor (TCR) gammadelta-positive T cells, increased immunoglobulin levels and retained ability for antibody production. Similar to originally reported patients with this newly recognized immune phenotype, our patient developed disseminated cytomegalovirus (CMV) infection and autoimmune cytopenia.
  
  
  CONCLUSIONS
  In infants with disseminated cytomegalovirus infection and autoimmune cytopenia, even if basic immunologic investigation appears normal, RAG1 immunodeficiency should be considered.
authors.affiliation: Departments of Paediatric Immunology, Pathology and Transfusion Medicine, Mother and Child Health Institute Dr Vukan Cupić, Belgrade, R. Dakica 8 Str., Serbia. pasics@ikomline.net
authors.forename: Srdjan
authors.initials: S
authors.lastname: Pasic
authors.forename: Slavisa
authors.initials: S
authors.lastname: Djuricic
authors.forename: Goran
authors.initials: G
authors.lastname: Ristic
authors.forename: Bojana
authors.initials: B
authors.lastname: Slavkovic
mesh_terms: D015703:Antigens, CD / Q000097:blood; D001344:Autopsy; D002675:Child, Preschool; D003241:Consanguinity; D017809:Fatal Outcome; D005260:Female; D016654:Genes, RAG-1 / Q000235:genetics*; D006801:Humans; D007223:Infant; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D009154:Mutation; D010641:Phenotype; D016511:Severe Combined Immunodeficiency / Q000097:blood / Q000235:genetics* / Q000276:immunology; D035781:Siblings
chemical_list: D015703:Antigens, CD