دورية أكاديمية
NUDCD3 deficiency disrupts V(D)J recombination to cause SCID and Omenn syndrome.
| العنوان: | NUDCD3 deficiency disrupts V(D)J recombination to cause SCID and Omenn syndrome. |
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| المؤلفون: | Chen R; Translational and Clinical Research Institute, Newcastle University, NE2 4HH Newcastle upon Tyne, UK., Lukianova E; Wellcome Sanger Institute, Wellcome Genome Campus, CB10 1SA Hinxton, UK., van der Loeff IS; Translational and Clinical Research Institute, Newcastle University, NE2 4HH Newcastle upon Tyne, UK.; Great North Children's Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, NE1 4LP Newcastle upon Tyne, UK., Spegarova JS; Translational and Clinical Research Institute, Newcastle University, NE2 4HH Newcastle upon Tyne, UK., Willet JDP; Translational and Clinical Research Institute, Newcastle University, NE2 4HH Newcastle upon Tyne, UK., James KD; Institute of Immunology and Immunotherapy, University of Birmingham. B15 2TT Birmingham, UK., Ryder EJ; Wellcome Sanger Institute, Wellcome Genome Campus, CB10 1SA Hinxton, UK., Griffin H; Translational and Clinical Research Institute, Newcastle University, NE2 4HH Newcastle upon Tyne, UK., IJspeert H; Department of Immunology, Erasmus University Medical Center, Rotterdam 3000 CA, Netherlands., Gajbhiye A; Biosciences Institute, Newcastle University, NE2 4HH Newcastle upon Tyne, UK., Lamoliatte F; Biosciences Institute, Newcastle University, NE2 4HH Newcastle upon Tyne, UK., Marin-Rubio JL; Biosciences Institute, Newcastle University, NE2 4HH Newcastle upon Tyne, UK., Woodbine L; Genome Damage and Stability Centre, University of Sussex, BN1 9RQ Brighton, UK., Lemos H; Translational and Clinical Research Institute, Newcastle University, NE2 4HH Newcastle upon Tyne, UK., Swan DJ; Translational and Clinical Research Institute, Newcastle University, NE2 4HH Newcastle upon Tyne, UK., Pintar V; Translational and Clinical Research Institute, Newcastle University, NE2 4HH Newcastle upon Tyne, UK., Sayes K; Translational and Clinical Research Institute, Newcastle University, NE2 4HH Newcastle upon Tyne, UK., Ruiz-Morales ER; Wellcome Sanger Institute, Wellcome Genome Campus, CB10 1SA Hinxton, UK., Eastham S; Wellcome Sanger Institute, Wellcome Genome Campus, CB10 1SA Hinxton, UK., Dixon D; Biosciences Institute, Newcastle University, NE2 4HH Newcastle upon Tyne, UK., Prete M; Wellcome Sanger Institute, Wellcome Genome Campus, CB10 1SA Hinxton, UK., Prigmore E; Wellcome Sanger Institute, Wellcome Genome Campus, CB10 1SA Hinxton, UK., Jeggo P; Genome Damage and Stability Centre, University of Sussex, BN1 9RQ Brighton, UK., Boyes J; Faculty of Biological Sciences, University of Leeds, LS2 9JT Leeds, UK., Mellor A; Translational and Clinical Research Institute, Newcastle University, NE2 4HH Newcastle upon Tyne, UK., Huang L; Translational and Clinical Research Institute, Newcastle University, NE2 4HH Newcastle upon Tyne, UK., van der Burg M; Department of Immunology, Erasmus University Medical Center, Rotterdam 3000 CA, Netherlands., Engelhardt KR; Translational and Clinical Research Institute, Newcastle University, NE2 4HH Newcastle upon Tyne, UK., Stray-Pedersen A; Norwegian National Unit for Newborn Screening, Division of Pediatric and Adolescent Medicine, Oslo University Hospital, Oslo 0424, Norway., Erichsen HC; Division of Pediatric and Adolescent Medicine, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo 0424, Norway., Gennery AR; Translational and Clinical Research Institute, Newcastle University, NE2 4HH Newcastle upon Tyne, UK.; Great North Children's Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, NE1 4LP Newcastle upon Tyne, UK., Trost M; Biosciences Institute, Newcastle University, NE2 4HH Newcastle upon Tyne, UK., Adams DJ; Wellcome Sanger Institute, Wellcome Genome Campus, CB10 1SA Hinxton, UK., Anderson G; Institute of Immunology and Immunotherapy, University of Birmingham. B15 2TT Birmingham, UK., Lorenc A; Wellcome Sanger Institute, Wellcome Genome Campus, CB10 1SA Hinxton, UK., Trynka G; Wellcome Sanger Institute, Wellcome Genome Campus, CB10 1SA Hinxton, UK.; Open Targets, Wellcome Genome Campus, CB10 1SA Hinxton, UK., Hambleton S; Translational and Clinical Research Institute, Newcastle University, NE2 4HH Newcastle upon Tyne, UK.; Great North Children's Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, NE1 4LP Newcastle upon Tyne, UK. |
| المصدر: | Science immunology [Sci Immunol] 2024 May 24; Vol. 9 (95), pp. eade5705. Date of Electronic Publication: 2024 May 24. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 101688624 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2470-9468 (Electronic) Linking ISSN: 24709468 NLM ISO Abbreviation: Sci Immunol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Washington, DC : American Association for the Advancement of Science, [2016]- |
| مواضيع طبية MeSH: | Severe Combined Immunodeficiency*/genetics , Severe Combined Immunodeficiency*/immunology , V(D)J Recombination*/immunology , V(D)J Recombination*/genetics, Humans ; Animals ; Mice ; Male ; Female ; Infant ; B-Lymphocytes/immunology ; Homeodomain Proteins/genetics ; Homeodomain Proteins/immunology ; T-Lymphocytes/immunology ; Child, Preschool ; Mutation, Missense |
| مستخلص: | Inborn errors of T cell development present a pediatric emergency in which timely curative therapy is informed by molecular diagnosis. In 11 affected patients across four consanguineous kindreds, we detected homozygosity for a single deleterious missense variant in the gene NudC domain-containing 3 ( NUDCD3 ) . Two infants had severe combined immunodeficiency with the complete absence of T and B cells (T - B - SCID), whereas nine showed classical features of Omenn syndrome (OS). Restricted antigen receptor gene usage by residual T lymphocytes suggested impaired V(D)J recombination. Patient cells showed reduced expression of NUDCD3 protein and diminished ability to support RAG-mediated recombination in vitro, which was associated with pathologic sequestration of RAG1 in the nucleoli. Although impaired V(D)J recombination in a mouse model bearing the homologous variant led to milder immunologic abnormalities, NUDCD3 is absolutely required for healthy T and B cell development in humans. |
| المشرفين على المادة: | 128559-51-3 (RAG-1 protein) 0 (Homeodomain Proteins) |
| تواريخ الأحداث: | Date Created: 20240524 Date Completed: 20240524 Latest Revision: 20240524 |
| رمز التحديث: | 20240525 |
| DOI: | 10.1126/sciimmunol.ade5705 |
| PMID: | 38787962 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 2470-9468 |
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| DOI: | 10.1126/sciimmunol.ade5705 |