title: Novel mutatıons and diverse clinical phenotypes in recombinase-activating gene 1 deficiency.
abstract: BACKGROUND
  Severe combined immunodeficiency is within a heterogeneous group of inherited defects throughout the development of T- and/or B-lymphocytes. Mutations in recombinase-activating genes 1 or 2 (RAG1/2) represent approximately 10% of all SCID cases. RAG1/2 are essential for V(D)J rearrangement of the B- and T-cell receptors.
  
  
  OBJECTIVE
  The aim of this study was to review clinical, immunological and molecular findings of Turkish SCID patients with RAG1 defects and to draw attention to novel mutations, genotype-phenotype correlations and the high rate of BCG infections within this group.
  
  
  METHODS
  Eleven patients (F/M: 6/5) were included. Molecular, immunological and clinical data were evaluated.
  
  
  RESULTS
  Five patients were classified as T-B-NK + SCID, four patients as T + B-NK + SCID (two of these patients were diagnosed as classical Omenn syndrome) and two patients as T + B + NK + SCID with respect to clinical presentations and immunological data. Mean age of the whole study group, mean age at onset of symptoms and mean age at diagnosis were: 33.0 ± 42.8, 3.1 ± 3.3 and 10.4 ± 13.5 months, respectively. Consanguinity rate was 54%. Some novel mutations were found in RAG1 gene in addition to previously reported mutations. Genotype-phenotype correlation was not significantly apparent in most of the cases. BCG infection was observed in 36.4% of patients (two BCG-osis and two BCG-itis).
  
  
  CONCLUSIONS
  Epigenetic factors such as compound genetic defects, enviromental factors, and exposure to recurrent infections may modify phenotypical characteristics of RAG deficiencies. Inoculation of live vaccines such as BCG should be postponed until primary immunodeficiency disease is excluded with appropriate screening tests in suspected cases.
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Ege University, 35100 Bornova, Izmir, Turkey.
authors.forename: Necil
authors.initials: N
authors.lastname: Kutukculer
authors.forename: Nesrin
authors.initials: N
authors.lastname: Gulez
authors.forename: Neslihan Edeer
authors.initials: NE
authors.lastname: Karaca
authors.forename: Guzide
authors.initials: G
authors.lastname: Aksu
authors.forename: Afig
authors.initials: A
authors.lastname: Berdeli
mesh_terms: D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology; D001500:BCG Vaccine; D003241:Consanguinity; D044127:Epigenesis, Genetic; D005260:Female; D016654:Genes, RAG-1 / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D009154:Mutation; D010641:Phenotype; D016511:Severe Combined Immunodeficiency / Q000145:classification / Q000235:genetics* / Q000276:immunology / Q000628:therapy; D013601:T-Lymphocytes / Q000276:immunology; D014421:Turkey
chemical_list: D001500:BCG Vaccine