title: RAG1 reversion mosaicism in a patient with Omenn syndrome.
abstract: OBJECTIVE
  To identify mechanisms of disease in a child born to consanguineous parents, who presented with Omenn syndrome (OS) and was found to carry a heterozygous RAG1 mutation in peripheral blood DNA.
  
  
  METHODS
  Mutation analysis was performed on whole blood and buccal swab DNA. Recombination activity of the mutant RAG1 protein and diversity of T cell repertoire were tested.
  
  
  RESULTS
  Apparent heterozygosity for a novel, functionally null RAG1 mutation in peripheral blood DNA from a patient with OS was shown to be secondary to true somatic reversion. Analysis of T cell repertoire demonstrated expression of various TCRBV families, but an overall restricted pattern.
  
  
  CONCLUSIONS
  This is the first case of true somatic reversion of a RAG1 mutation in a patient with OS. The reversion event likely occurred at a stage where only a limited pool of T cell progenitors capable of performing V(D)J recombination could be generated. This work emphasizes the importance of performing functional studies to investigate the significance of novel genetic variants, and to consider somatic reversion as a possible disease modifier in SCID.
authors.affiliation: Division of Immunology, Boston Children's Hospital, Karp Research Building, Room 10217, 1, Blackfan Circle, Boston, MA, 02115, USA.
authors.forename: Elena
authors.initials: E
authors.lastname: Crestani
authors.forename: Sharon
authors.initials: S
authors.lastname: Choo
authors.forename: Francesco
authors.initials: F
authors.lastname: Frugoni
authors.forename: Yu Nee
authors.initials: YN
authors.lastname: Lee
authors.forename: Stephanie
authors.initials: S
authors.lastname: Richards
authors.forename: Joanne
authors.initials: J
authors.lastname: Smart
authors.forename: Luigi D
authors.initials: LD
authors.lastname: Notarangelo
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D004252:DNA Mutational Analysis; D005838:Genotype; D018380:Hematopoietic Stem Cell Transplantation; D006579:Heterozygote; D018398:Homeodomain Proteins / Q000097:blood / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D009030:Mosaicism; D016511:Severe Combined Immunodeficiency / Q000235:genetics* / Q000276:immunology / Q000473:pathology / Q000628:therapy; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D019895:Transposases / Q000097:blood / Q000235:genetics*
chemical_list: D018398:Homeodomain Proteins; C064658:RAG-1 protein; D019895:Transposases