ArticleProceedings of the National Academy of Sciences of the United States of America2000
N-terminal RAG1 frameshift mutations in Omenn's syndrome: internal methionine usage leads to partial V(D)J recombination activity and reveals a fundamental role in vivo for the N-terminal domains.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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39 citing papers in PubMed, 68 citations in OpenAlex.
- Article
- Generation of antigen-specific mature T cells from RAG1Nature biomedical engineering · 2024Article
- Exonic knockout and knockin gene editing in hematopoietic stem and progenitor cells rescues RAG1 immunodeficiency.Science translational medicine · 2024Article
- Quantitative determination of SLC2A1 variant functional effects in GLUT1 deficiency syndrome.Annals of clinical and translational neurology · 2023Article
- Downstream Alternate Start Site Allows N-Terminal Nonsense Variants to Escape NMD and Results in Functional Recovery by Readthrough and Modulator Combination.Journal of personalized medicine · 2022Article
- Clinical, Immunological, and Molecular Variability of RAG Deficiency: A Retrospective Analysis of 22 RAG Patients.Journal of clinical immunology · 2022Article
- RAG gene defects at the verge of immunodeficiency and immune dysregulation.Immunological reviews · 2019Review
- Early-onset inflammatory bowel disease as a model disease to identify key regulators of immune homeostasis mechanisms.Immunological reviews · 2019Review
- A purely quantitative form of partial recessive IFN-γR2 deficiency caused by mutations of the initiation or second codon.Human molecular genetics · 2018Article
- Capitalizing on the heterogeneous effects of CFTR nonsense and frameshift variants to inform therapeutic strategy for cystic fibrosis.PLoS genetics · 2018Article
- RAG Deficiency: Two Genes, Many Diseases.Journal of clinical immunology · 2018Review
- Characterization of an N-Terminal Non-Core Domain of RAG1 Gene Disrupted Syrian Hamster Model Generated by CRISPR Cas9.Viruses · 2018Article
- Illegitimate translation causes unexpected gene expression from on-target out-of-frame alleles created by CRISPR-Cas9.Scientific reports · 2016Article
- Article
- Human RAG mutations: biochemistry and clinical implications.Nature reviews. Immunology · 2016Review
- Article
- Co-existence of clonal expanded autologous and transplacental-acquired maternal T cells in recombination activating gene-deficient severe combined immunodeficiency.Clinical and experimental immunology · 2014Article
- Similar recombination-activating gene (RAG) mutations result in similar immunobiological effects but in different clinical phenotypes.The Journal of allergy and clinical immunology · 2014Article
- Article
- Adult-onset manifestation of idiopathic T-cell lymphopenia due to a heterozygous RAG1 mutation.The Journal of allergy and clinical immunology · 2013Article
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9 authors at 1 institution in 1 country.
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Abstract
Omenn's syndrome is an autosomal recessive primary immunodeficiency characterized by variable numbers of T lymphocytes of limited clonality, hypereosinophilia, and high IgE levels with a paradoxical absence of circulating B lymphocytes. We have previously attributed this disorder to missense mutations that render the RAG1/RAG2 recombinase only partially active. Here we report seven Omenn's patients with a novel class of genetic lesions: frameshift mutations within the 5' coding region of RAG1. Interestingly, we demonstrate in transient expression experiments that these frameshift deletion alleles remain partially functional for both deletional and inversional recombination and can hence explain the partial rearrangement phenotype observed in these patients. The rearrangement activity is mediated by truncated RAG1 proteins that are generated by alternative ATG usage 3' to the frameshift deletion and that demonstrate improper cellular localization. Taken together, our results suggest a novel mechanism for the development of immunodeficiency in a subset of Omenn's syndrome patients.
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