Oligoclonal expansion of T lymphocytes with multiple second-site mutations leads to Omenn syndrome in a patient with RAG1-deficient severe combined immunodeficiency
Open Access
- 15 September 2005
- journal article
- case report
- Published by American Society of Hematology in Blood
- Vol. 106 (6) , 2099-2101
- https://doi.org/10.1182/blood-2005-03-0936
Abstract
Omenn syndrome (OS) is a rare primary immunodeficiency characterized by the presence of activated/oligoclonal T cells, eosinophilia, and the absence of circulating B cells. OS patients carry leaky mutations of recombination activating genes (RAG1 or RAG2) resulting in partial V(D)J recombination activity, whereas null mutations cause severe combined immunodeficiency with absence of mature T and B cells (T-B- SCID). Here we describe somatic mosaicism due to multiple second-site mutations in a patient with RAG1 deficiency. We found that he is homozygous for a single base deletion in the RAG1 gene, which results in frameshift and likely abrogates the protein function. However, the patient showed typical OS features. Molecular analysis revealed that several second-site mutations, all of which restored the RAG1 reading frame and resulted in missense mutations, were demonstrated in his T cells. These findings suggest that his revertant T-cell mosaicism is responsible for OS phenotype switched from T-B- SCID. (Blood. 2005; 106:2099-2101)Keywords
This publication has 18 references indexed in Scilit:
- Oligoclonal expansion of circulating and tissue-infiltrating CD8+ T Cells with killer/effector phenotypes in juvenile dermatomyositis syndromeClinical and Experimental Immunology, 2004
- Differential contribution of Wiskott-Aldrich syndrome protein to selective advantage in T- and B-cell lineagesBlood, 2004
- In vivo reversion to normal of inherited mutations in humansJournal of Medical Genetics, 2003
- CD8αα memory effector T cells descend directly from clonally expanded CD8α+βhigh TCRαβ T cells in vivoBlood, 2002
- Identical mutations in RAG1 or RAG2 genes leading to defective V(D)J recombinase activity can cause either T-B–severe combined immune deficiency or Omenn syndromeBlood, 2001
- V(D)J recombination defects in lymphocytes due to RAG mutations: severe immunodeficiency with a spectrum of clinical presentationsBlood, 2001
- Spontaneous in vivo reversion to normal of an inherited mutation in a patient with adenosine deaminase deficiencyNature Genetics, 1996
- RAG-2-deficient mice lack mature lymphocytes owing to inability to initiate V(D)J rearrangementCell, 1992
- RAG-1-deficient mice have no mature B and T lymphocytesCell, 1992
- Combined immunodeficiency and reticuloendotheliosis with eosinophiliaThe Journal of Pediatrics, 1974