title: A hypomorphic recombination-activating gene 1 (RAG1) mutation resulting in a phenotype resembling common variable immunodeficiency.
abstract: BACKGROUND
  Recombination-activating gene 1 (RAG1) deficiency presents with a varied spectrum of combined immunodeficiency, ranging from a T(-)B(-)NK(+) type of disease to a T(+)B(+)NK(+) phenotype.
  
  
  OBJECTIVE
  We sought to assess the genetic background of patients with common variable immunodeficiency (CVID).
  
  
  METHODS
  A patient given a diagnosis of CVID, who was born to a consanguineous family and thus would be expected to show an autosomal recessive inheritance, was subjected to clinical evaluation, immunologic assays, homozygosity gene mapping, exome sequencing, Sanger sequencing, and functional analysis.
  
  
  RESULTS
  The 14-year-old patient, who had liver granuloma, extranodal marginal zone B-cell lymphoma, and autoimmune neutropenia, presented with a clinical picture resembling CVID. Genetic analysis of this patient showed a homozygous hypomorphic RAG1 mutation (c.1073 G>A, p.C358Y) with a residual functional capacity of 48% of wild-type protein.
  
  
  CONCLUSIONS
  Our finding broadens the range of disorders associated with RAG1 mutations and might have important therapeutic implications.
authors.affiliation: Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institute at Karolinska University Hospital Huddinge, Stockholm, Sweden; Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Science, Tehran, Iran.
authors.forename: Hassan
authors.initials: H
authors.lastname: Abolhassani
authors.affiliation: Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institute at Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.affiliation: Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Science, Tehran, Iran.
authors.forename: Asghar
authors.initials: A
authors.lastname: Aghamohammadi
authors.affiliation: Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Science, Tehran, Iran.
authors.forename: Nima
authors.initials: N
authors.lastname: Rezaei
authors.affiliation: Division of Immunology and the Manton Center for Orphan Disease Research, Boston Children's Hospital, and the Harvard Stem Cell Institute, Harvard Medical School, Boston, Mass.
authors.forename: Yu Nee
authors.initials: YN
authors.lastname: Lee
authors.affiliation: Division of Immunology and the Manton Center for Orphan Disease Research, Boston Children's Hospital, and the Harvard Stem Cell Institute, Harvard Medical School, Boston, Mass.
authors.forename: Francesco
authors.initials: F
authors.lastname: Frugoni
authors.affiliation: Division of Immunology and the Manton Center for Orphan Disease Research, Boston Children's Hospital, and the Harvard Stem Cell Institute, Harvard Medical School, Boston, Mass.
authors.forename: Luigi D
authors.initials: LD
authors.lastname: Notarangelo
authors.affiliation: Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institute at Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Pan-Hammarström
authors.affiliation: Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institute at Karolinska University Hospital Huddinge, Stockholm, Sweden. Electronic address: lennart.hammarstrom@ki.se.
authors.forename: Lennart
authors.initials: L
authors.lastname: Hammarström
mesh_terms: D000293:Adolescent; D017074:Common Variable Immunodeficiency / Q000235:genetics* / Q000276:immunology; D006099:Granuloma / Q000235:genetics / Q000276:immunology; D018398:Homeodomain Proteins / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D008107:Liver Diseases / Q000235:genetics / Q000276:immunology; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000276:immunology; D008297:Male; D009154:Mutation; D009503:Neutropenia / Q000235:genetics / Q000276:immunology; D010641:Phenotype
chemical_list: D018398:Homeodomain Proteins; C064658:RAG-1 protein
keywords: Common variable immunodeficiency; differential diagnosis; granulomatous lesion; mismanagement; recombination activation genes