Omenn's syndrome occurring in patients without mutations in recombination activating genes

Andrew R. Gennery, Elizabeth Hodges, Anthony P. Williams, Susan Harris, Anna Villa, Brian Angus, Andrew J. Cant, John L. Smith

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)246-256
Number of pages11
JournalClinical Immunology
Volume116
Issue number3
DOIs
Publication statusPublished - Sep 2005

Keywords

  • Artemis gene
  • Omenn syndrome
  • Recombination activating gene
  • T cell receptor oligoclonality

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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