Genetic screening of male patients with primary hypogammaglobulinemia can guide diagnosis and clinical management
| Autor: | Ioannis Theodorou, Nicolas Vince, Patrice Debré, Gael Mouillot, Angélique Guignet, Sophie Limou, Eric Oksenhendler, Marion Malphettes, Claire Fieschi, Pierre-Antoine Gourraud, Véronique Bertrand, David Boutboul, Philippe Pellet |
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| Přispěvatelé: | Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Immunité et Infection, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR113-Université Pierre et Marie Curie - Paris 6 (UPMC), Service d'Immunopathologie [Hôpital Saint-Louis, Paris], Université Paris Diderot - Paris 7 (UPD7)-Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), École Centrale de Nantes (ECN), Différenciation des cellules B, hémopathies, lymphoïdes et déficit de l'immunité humorale, Université Paris Diderot - Paris 7 (UPD7), Department of Clinical Immunology, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Université Paris Diderot - Paris 7 (UPD7)-CHU Saint Louis [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP) |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Recombinant Fusion Proteins Genetic counseling DNA Mutational Analysis Immunology Genetic Counseling medicine.disease_cause Monocytes Hypogammaglobulinemia 03 medical and health sciences Agammaglobulinemia hemic and lymphatic diseases Agammaglobulinaemia Tyrosine Kinase medicine Humans Immunology and Allergy Bruton's tyrosine kinase Immunodeficiency CD40L Genetic Testing Signaling Lymphocytic Activation Molecule Associated Protein Genetic testing Mutation medicine.diagnostic_test biology business.industry Common variable immunodeficiency CVID Infant [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology General Medicine Protein-Tyrosine Kinases medicine.disease Phenotype 3. Good health 030104 developmental biology [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics BTK Child Preschool biology.protein [SDV.IMM]Life Sciences [q-bio]/Immunology business SAP Biomarkers |
| Zdroj: | Human Immunology Human Immunology, Elsevier, 2018, 79 (7), pp.571-577. ⟨10.1016/j.humimm.2018.04.014⟩ |
| ISSN: | 0198-8859 |
| DOI: | 10.1016/j.humimm.2018.04.014⟩ |
| Popis: | International audience; The precise diagnosis of an immunodeficiency is sometimes difficult to assess, especially due to the large spectrum of phenotypic variation reported among patients. Common variable immunodeficiency disorders (CVID) do not have, for a large part, an identified genetic cause. The identification of a causal genetic mutation is important to confirm, or in some cases correct, the diagnosis. We screened >150 male patients with hypogammaglobulinemia for mutations in three genes involved in pediatric X-linked primary immunoglobulin deficiency: CD40LG, SH2D1A and BTK. The SH2D1A screening allowed to reclassify two individuals with an initial CVID presentation as XLP after mutations identification. All these mutations were associated with a lack of protein expression. In addition, 4 patients with a primary diagnosis of CVID and one with a primary IgG subclass deficiency were requalified as XLA after identifying BTK mutations. Interestingly, two out of these 5 patients carried a damaging coding BTK mutation associated with a lower, but detectable, BTK expression in monocytes, suggesting that a dysfunctional protein explains the disease phenotype in these patients. In conclusion, our results advocate to include SH2D1A and BTK in newly developed targeted NGS genetic testing, to contribute to providing the most appropriate medical treatment and genetic counselling. |
| Databáze: | OpenAIRE |
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