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.
| Original language | English |
|---|---|
| Pages (from-to) | 2099-2101 |
| Number of pages | 3 |
| Journal | Blood |
| Volume | 106 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Sep 15 2005 |
| Externally published | Yes |
Fingerprint
ASJC Scopus subject areas
- Hematology
Cite this
Oligoclonal expansion of T lymphocytes with multiple second-site mutations leads to Omenn syndrome in a patient with RAG1-deficient severe combined immunodeficiency. / Wada, Taizo; Toma, Tomoko; Okamoto, Hiroyuki; Kasahara, Yoshihito; Koizumi, Shoichi; Agematsu, Kazunaga; Kimura, Hirokazu; Shimada, Akira; Hayashi, Yasuhide; Kato, Masahiko; Yachie, Akihiro.
In: Blood, Vol. 106, No. 6, 15.09.2005, p. 2099-2101.Research output: Contribution to journal › Article
}
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.
UR - http://www.scopus.com/inward/record.url?scp=24744460541&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=24744460541&partnerID=8YFLogxK
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 -