Severe combined immunodeficiency with sensitivity to ionizing radiation

05/01/2015 - "Our results demonstrate that gene editing in RS-SCID fibroblasts rescued DNA-PK dependent signaling to overcome radiosensitivity. "
08/01/2012 - "RS SCID forms are caused by defects in the NHEJ pathway, the enzymatic process required for the repair of DNA double-strand breaks. "
10/22/2009 - "Likewise, significant increase in DNA microhomology usage is the signature of CSR junctions obtained from human RS-SCID patients harboring hypomorphic Artemis mutations. "
03/01/2000 - "A human SCID condition is also characterized by an absence of mature T and B lymphocytes, and is associated with an increase in sensitivity to DNA-damaging agents (RS-SCID). "
05/01/1996 - "We therefore conclude that some human T-B-RS SCID disorders are not caused by a defect in an essential DNA-PK component."

01/01/2022 - "All of the findings are useful in explaining how a hypomorphic L3062R missense mutation of DNA-PKcs could lead to insufficient Artemis activation, hence RS-SCID. "
01/01/2009 - "Here we have identified the first human RS-SCID patient to our knowledge with a DNA-PKcs missense mutation (L3062R). "
01/01/2009 - "This study demonstrates that the presence of DNA-PKcs kinase activity is not sufficient to rule out a defect in this gene during diagnosis and treatment of RS-SCID patients. "

05/01/2015 - "In this study, we established zinc-finger nuclease-mediated genome editing in primary fibroblasts and iPSCs generated from a mouse model for radiosensitive severe combined immunodeficiency (RS-SCID), a rare disorder characterized by cellular sensitivity to radiation and the absence of lymphocytes due to impaired DNA-dependent protein kinase (DNA-PK) activity. "

01/01/2009 - "This study demonstrates that the presence of DNA-PKcs kinase activity is not sufficient to rule out a defect in this gene during diagnosis and treatment of RS-SCID patients. "

05/01/2015 - "In this study, we established zinc-finger nuclease-mediated genome editing in primary fibroblasts and iPSCs generated from a mouse model for radiosensitive severe combined immunodeficiency (RS-SCID), a rare disorder characterized by cellular sensitivity to radiation and the absence of lymphocytes due to impaired DNA-dependent protein kinase (DNA-PK) activity. "

04/20/2001 - "We herein describe the cloning of the gene encoding a novel protein involved in V(D)J recombination/DNA repair, Artemis, whose mutations cause human RS-SCID. "
08/01/2004 - "Radiosensitive severe combined immunodeficiency (RS-SCID) is caused by mutations in Artemis, a protein that plays a subsidiary role in non-homologous end-joining although it is not an essential component. "
07/01/2015 - "There is evidence for the involvement of Artemis endonuclease, a protein deficient in a human radiosensitivity syndrome associated with severe immunodeficiency (RS-SCID), in the processing of subsets of DSBs by HRR or C-NHEJ. "
04/01/2003 - "A subgroup of patients with severe combined immunodeficiency (SCID) and increased cellular radiation sensitivity (RS-SCID) have mutations of Artemis, a gene that encodes a protein essential for V(D)J recombination and DNA double-strand break repair. "
09/01/2011 - "Ataxia telangiectasia (ATM) mutated and Artemis, the proteins defective in ataxia telangiectasia and a class of Radiosensitive-Severe Combined Immunodeficiency (RS-SCID), respectively, function in the repair of DNA double strand breaks (DSBs), which arise in heterochromatic DNA (HC-DSBs) following exposure to ionizing radiation (IR). "

04/04/2010 - "Together these results indicate a novel class of RS-SCID patients characterized by the specific absence of T lymphocytes and associated with defects in G(2)-specific DSB repair. "
02/15/2003 - "Some T(-)B(-)NK(+) SCID patients without RAG gene mutations are sensitive to ionizing radiation, and several of these radiosensitive (RS) SCID patients were recently shown to have large deletions or truncation mutations in the Artemis gene, implying a role for Artemis in DNA double-strand break (dsb) repair. "
05/01/1996 - "We show here that cells from six patients with T-B-RS SCID had normal DNA-dsb repair kinetics. "
12/03/2004 - "By epistasis analysis, we show that ataxia telangiectasia mutated protein (ATM) and Artemis, the protein defective in patients with RS-SCID, function in a common double-strand break (DSB) repair pathway that also requires H2AX, 53BP1, Nbs1, Mre11, and DNA-PK. "

02/15/2003 - "Immunogenotyping and immunophenotyping of bone marrow samples of 2 RS-SCID patients showed the absence of complete V(H)-J(H) gene rearrangements and consequently a complete B-cell differentiation arrest at the pre-B-cell receptor checkpoint-that is, at the transition from CyIgmu(-) pre-B-I cells to CyIgmu(+) pre-B-II cells. "

01/01/2009 - "Here we have identified the first human RS-SCID patient to our knowledge with a DNA-PKcs missense mutation (L3062R). "

12/13/2019 - "A lentiviral vector expressing physiological levels of human ARTEMIS mRNA from an EF1a promoter without post-transcriptional regulation was developed as a safe clinically applicable candidate for RS-SCID gene therapy. "

01/01/2020 - "Diagnosis of radiosensitive severe combined immunodeficiency disease (RS-SCID) by Comet Assay, management of bone marrow transplantation."

10/31/2006 - "Overall, the results indicate that a gene therapy approach for RS-SCID involving the transplantation of genetically modified HSCs is indeed feasible. "

10/31/2006 - "To establish the feasibility of a gene therapy approach to the treatment of RS-SCID, we generated a series of lentiviral vectors expressing human Artemis from different promoters and used them to transduce highly purified hematopoietic stem cells (HSCs) from Artemis knockout mice. "
10/31/2006 - "Overall, the results indicate that a gene therapy approach for RS-SCID involving the transplantation of genetically modified HSCs is indeed feasible. "