title: Omenn's syndrome occurring in patients without mutations in recombination activating genes.
abstract: Omenn syndrome (OS) is characterised by hepatosplenomegaly, lymphadenopathy, erythema, eosinophilia, elevated IgE, oligoclonal T cell expansions and recombinase activating gene (RAG) mutations. We investigated 9 cases of OS to correlate genotype with immunophenotype using a two-color flow cytometry with monoclonal antibodies against CD3 and TCRVB families to map TCRVB usage. T and B clonal cell populations were examined in peripheral blood lymphocytes by PCR and sequencing of TCRB/TCRG T cell and IGH FR2/FR3 B cell products. RAG and Artemis genes were sequenced from genomic DNA. All patients demonstrated absent TCRVB families; six had predominant TCRVB families, six oligoclonal TCR gene rearrangements including TCRGD rearrangements. One demonstrated functional IGH rearrangement, an observation not previously reported. In this clinically homogeneous population, with similar immunological phenotype, RAG mutations were identified in only 2/9 patients. OS is a genetically heterogeneous condition, and patients with similar immunophenotypes may have as yet unidentified gene defects.
authors.affiliation: Department of Paediatrics, Newcastle General Hospital, Westgate Road, Newcastle-upon-Tyne NE4 6BE, UK. A.R.Gennery@ncl.ac.uk
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Gennery
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Hodges
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Williams
authors.forename: Susan
authors.initials: S
authors.lastname: Harris
authors.forename: Anna
authors.initials: A
authors.lastname: Villa
authors.forename: Brian
authors.initials: B
authors.lastname: Angus
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Cant
authors.forename: John L
authors.initials: JL
authors.lastname: Smith
mesh_terms: D001483:Base Sequence; D004247:DNA / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D004720:Endonucleases; D005260:Female; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D015334:Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor; D005838:Genotype; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D016511:Severe Combined Immunodeficiency / Q000235:genetics* / Q000276:immunology; D013577:Syndrome
chemical_list: D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; C499311:RAG2 protein, human; C064655:V(D)J recombination activating protein 2; C064658:RAG-1 protein; D004247:DNA; C426344:DCLRE1C protein, human; D004720:Endonucleases