TY - JOUR
T1 - Oligoclonal expansion of T lymphocytes with multiple second-site mutations leads to Omenn syndrome in a patient with RAG1-deficient severe combined immunodeficiency
AU - Wada, Taizo
AU - Toma, Tomoko
AU - Okamoto, Hiroyuki
AU - Kasahara, Yoshihito
AU - Koizumi, Shoichi
AU - Agematsu, Kazunaga
AU - Kimura, Hirokazu
AU - Shimada, Akira
AU - Hayashi, Yasuhide
AU - Kato, Masahiko
AU - Yachie, Akihiro
PY - 2005/9/15
Y1 - 2005/9/15
N2 - 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.
AB - 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.
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U2 - 10.1182/blood-2005-03-0936
DO - 10.1182/blood-2005-03-0936
M3 - Article
C2 - 15845893
AN - SCOPUS:24744460541
VL - 106
SP - 2099
EP - 2101
JO - Blood
JF - Blood
SN - 0006-4971
IS - 6
ER -