Human DOCK2 Deficiency: Report of a Novel Mutation and Evidence for Neutrophil Dysfunction
| Autor: | Sofie Struyf, Sophie Maebe, Ulrich Siler, Alejandro Nieto-Patlán, Benoit Florkin, Djalila Mekahli, Giorgia Bucciol, Jean-Laurent Casanova, Oleksandr Pastukhov, Helena Flipts, Isabelle Meyts, Jacinta Bustamante, François Vermeulen, Pierre Philippet, Luigi D. Notarangelo, Despina Moshous, Janine Reichenbach, Bertrand Boisson, Barbara Bosch, Anniek Corveleyn, Mieke Gouwy, Lars Desmet, Stuart G. Tangye, Leen Moens |
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| Přispěvatelé: | University of Zurich, Meyts, Isabelle |
| Rok vydání: | 2018 |
| Předmět: |
neutrophil dysfunction
Neutrophils Immunology 610 Medicine & health Biology medicine.disease_cause Article medicine Immunology and Allergy Guanine Nucleotide Exchange Factors Humans Immunodeficiency Sequence Deletion Severe combined immunodeficiency Mutation 2403 Immunology B-Lymphocytes Dock2 Alternative splicing GTPase-Activating Proteins DOCK2 11359 Institute for Regenerative Medicine (IREM) Actin cytoskeleton medicine.disease Omenn syndrome Pedigree Rac GTP-Binding Proteins Killer Cells Natural Alternative Splicing Oxidative Stress 10036 Medical Clinic biology.protein Cancer research 2723 Immunology and Allergy Severe Combined Immunodeficiency |
| Zdroj: | Journal of clinical immunology. 39(3) |
| ISSN: | 1573-2592 |
| Popis: | DOCK2 is a guanine-nucleotide-exchange factor for Rac proteins. Activated Rac serves various cellular functions including the reorganization of the actin cytoskeleton in lymphocytes and neutrophils and production of reactive oxygen species in neutrophils. Since 2015, six unrelated patients with combined immunodeficiency and early-onset severe viral infections caused by bi-allelic loss-of-function mutations in DOCK2 have been described. Until now, the function of phagocytes, specifically neutrophils, has not been assessed in human DOCK2 deficiency. Here, we describe a new kindred with four affected siblings harboring a homozygous splice-site mutation (c.2704-2 A > C) in DOCK2. The mutation results in alternative splicing and a complete loss of DOCK2 protein expression. The patients presented with leaky severe combined immunodeficiency or Omenn syndrome. The novel mutation affects EBV-B cell migration and results in NK cell dysfunction similar to previous observations. Moreover, both cytoskeletal rearrangement and reactive oxygen species production are partially impaired in DOCK2-deficient neutrophils. ispartof: JOURNAL OF CLINICAL IMMUNOLOGY vol:39 issue:3 pages:298-308 ispartof: location:Netherlands status: published |
| Databáze: | OpenAIRE |
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