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Blood, 1 June 2005, Vol. 105, No. 11, pp. 4179-4186. Prepublished online as a Blood First Edition Paper on February 24, 2005; DOI 10.1182/blood-2004-12-4861. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: 2004-12-4861v1 105/11/4179    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Ege, M. Articles by Pannicke, U. Search for Related Content PubMed PubMed Citation Articles by Ege, M. Articles by Pannicke, U. Related Collections Immunobiology Plenary Papers Free Research Articles Clinical Trials and Observations Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PLENARY PAPERS Omenn syndrome due to ARTEMIS mutations Markus Ege, Yunmei Ma, Burkhard Manfras, Krzysztof Kalwak, Haihui Lu, Michael R. Lieber, Klaus Schwarz, and Ulrich Pannicke From the Department of Transfusion Medicine, the University Children's Hospital, and the Division of Infectious Diseases and Clinical Immunology, the Department of Internal Medicine, The University Hospital Ulm, and the Institute for Clinical Transfusion Medicine and Immunogenetics, Ulm, Germany; the Norris Comprehensive Cancer Center, Departments of Pathology, Biochemistry and Molecular Biology, Biological Sciences, and Molecular Microbiology and Immunology, Los Angeles, CA; and the Department of Pediatric Hematology/Oncology and Bone Marrow Transplantation (BMT), The Wroclaw Medical University, Wroclaw, Poland. Omenn syndrome (OS) is characterized by severe combined immunodeficiency (SCID) associated with erythrodermia, hepatosplenomegaly, lymphadenopathy, and alopecia. In patients with OS, B cells are mostly absent, T-cell counts are normal to elevated, and T cells are frequently activated and express a restricted T-cell receptor (TCR) repertoire. Thus far, inherited hypomorphic mutations of the recombination activating genes 1 and 2 (RAG1/2) have been described in OS. We report on a first patient with clinical and immunologic features of OS caused by hypomorphic ARTEMIS mutations. The patient's T cells expressed / receptors with an oligoclonal repertoire but normal V(D)J recombination coding joints. Sequencing of the ARTEMIS gene revealed a compound heterozygosity in this nonhomologous end-joining (NHEJ) factor, explaining the enhanced radiosensitivity of the patient's primary dermal fibroblasts. The maternal allele contained a null mutation within the active center, whereas the expression of the paternal allele with a start codon (AUG to ACG) mutation partially restored V(D)J recombination and ARTEMIS function in vivo and in vitro. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Omenn syndrome: more than a disorder of RAG1 or RAG2 genes Marina Cavazzana-Calvo and Jean-Pierre de Villartay Blood 2005 105: 4156. [Full Text] [PDF] This article has been cited by other articles: L. Du, M. van der Burg, S. W. Popov, A. Kotnis, J. J.M. van Dongen, A. R. Gennery, and Q. Pan-Hammarstrom Involvement of Artemis in nonhomologous end-joining during immunoglobulin class switch recombination J. Exp. Med., December 22, 2008; 205(13): 3031 - 3040. [Abstract] [Full Text] [PDF] C. Simkus, P. Anand, A. Bhattacharyya, and J. M. Jones Biochemical and Folding Defects in a RAG1 Variant Associated with Omenn Syndrome J. Immunol., December 15, 2007; 179(12): 8332 - 8340. [Abstract] [Full Text] [PDF] D. Niewolik, U. Pannicke, H. Lu, Y. Ma, L.-C. V. Wang, P. Kulesza, E. Zandi, M. R. Lieber, and K. Schwarz DNA-PKcs Dependence of Artemis Endonucleolytic Activity, Differences between Hairpins and 5' or 3' Overhangs J. Biol. Chem., November 10, 2006; 281(45): 33900 - 33909. [Abstract] [Full Text] [PDF] A. R. Gennery Primary immunodeficiency syndromes associated with defective DNA double-strand break repair Br. Med. Bull., October 5, 2006; (2006) ldl006v2. [Abstract] [Full Text] [PDF] R. D. Kennedy and A. D. D'Andrea DNA Repair Pathways in Clinical Practice: Lessons From Pediatric Cancer Susceptibility Syndromes J. Clin. Oncol., August 10, 2006; 24(23): 3799 - 3808. [Abstract] [Full Text] [PDF] P. M. Evans, L. Woodbine, E. Riballo, A. R. Gennery, M. Hubank, and P. A. Jeggo Radiation-induced delayed cell death in a hypomorphic Artemis cell line Hum. Mol. Genet., April 15, 2006; 15(8): 1303 - 1311. [Abstract] [Full Text] [PDF] A. Enders, P. Fisch, K. Schwarz, U. Duffner, U. Pannicke, E. Nikolopoulos, A. Peters, M. Orlowska-Volk, D. Schindler, W. Friedrich, et al. A Severe Form of Human Combined Immunodeficiency Due to Mutations in DNA Ligase IV. J. Immunol., April 15, 2006; 176(8): 5060 - 5068. [Abstract] [Full Text] [PDF]

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