Compound heterozygous mutation of Rag1 leading to Omenn syndrome.
Compound heterozygous mutation of Rag1 leading to Omenn syndrome.
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DOI：
10.1371/journal.pone.0121489
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Butte MJ
中科院分区：
文献类型：
--
作者：
Matthews AG;Briggs CE;Yamanaka K;Small TN;Mooster JL;Bonilla FA;Oettinger MA;Butte MJ
Omenn syndrome is a primary immunodeficiency disorder, featuring susceptibility to infections and autoreactive T cells and resulting from defective genomic rearrangement of genes for the T cell and B cell receptors. The most frequent etiologies are hypomorphic mutations in “non-core” regions of the Rag1 or Rag2 genes, the protein products of which are critical members of the cellular apparatus for V(D)J recombination. In this report, we describe an infant with Omenn syndrome with a previously unreported termination mutation (p.R142*) in Rag1 on one allele and a partially characterized substitution mutation (p.V779M) in a “core” region of the other Rag1 allele. Using a cellular recombination assay, we found that while the p.R142* mutation completely abolished V(D)J recombination activity, the p.V779M mutation conferred a severe, but not total, loss of V(D)J recombination activity. The recombination defect of the V779 mutant was not due to overall misfolding of Rag1, however, as this mutant supported wild-type levels of V(D)J cleavage. These findings provide insight into the role of this poorly understood region of Rag1 and support the role of Rag1 in a post-cleavage stage of recombination.
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