Involvement of the Same TNFR1 Residue in Mendelian and Multifactorial Inflammatory Disorders
| Autor: | Sonia Karabina, Maria Teresa Mitjavila Garcia, Véronique Hentgen, Catherine Dodé, Gaëlle Le Borgne, Jacques Gaillat, Serge Charmion, Emmanuelle Cochet, Peter Lohse, Bruno Copin, Isabelle Jéru, Philippe Duquesnoy, Pascal Cathébras, Serge Amselem |
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| Přispěvatelé: | Physiopathologie des maladies génétiques d'expression pédiatrique, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Modèles de Cellules Souches Malignes et Thérapeutiques, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pitié-Salpêtrière [AP-HP], Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University-Hospital Munich-Großhadern [München], Centre de Référence des Maladies Auto-Inflammatoires et des Amyloses [CH Versailles] (CeRéMAIA - Hôpital André Mignot), Centre Hospitalier de Versailles André Mignot (CHV), Service de génétique et embryologie médicales [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Saint-Etienne, Departement Hospitalo- Universitaire - Inflammation, Immunopathologie, Biothérapie [Paris] (DHU - I2B), Université Pierre et Marie Curie - Paris 6 (UPMC)-CHU Pitié-Salpêtrière [AP-HP], Couvet, Sandrine |
| Rok vydání: | 2013 |
| Předmět: |
Male
Heredity Arginine [SDV]Life Sciences [q-bio] lcsh:Medicine [SDV.GEN] Life Sciences [q-bio]/Genetics Polymerase Chain Reaction Protein structure Genotype Missense mutation lcsh:Science Child Receptor Genetics Multidisciplinary Flow Cytometry Penetrance Innate Immunity Pedigree [SDV] Life Sciences [q-bio] Protein Transport Autosomal Dominant Receptors Tumor Necrosis Factor Type I Medicine [SDV.IMM]Life Sciences [q-bio]/Immunology Female Research Article Adult [SDV.IMM] Life Sciences [q-bio]/Immunology Adolescent In silico Immunology Blotting Western Static Electricity Mutation Missense Enzyme-Linked Immunosorbent Assay Gastroenterology and Hepatology Biology Molecular Genetics Young Adult Rheumatology Genetic Mutation Humans Inflammation [SDV.GEN]Life Sciences [q-bio]/Genetics lcsh:R Hereditary Autoinflammatory Diseases HEK 293 cells Mutation Types Immunity Human Genetics Molecular biology Genetics of Disease lcsh:Q Clinical Immunology |
| Zdroj: | PLoS ONE PLoS ONE, 2013, 8 (7), pp.e69757. ⟨10.1371/journal.pone.0069757⟩ PLoS ONE, Vol 8, Iss 7, p e69757 (2013) |
| ISSN: | 1932-6203 |
| Popis: | International audience; Objectives: TNFRSF1A is involved in an autosomal dominant autoinflammatory disorder called TNFR-associated periodic syndrome (TRAPS). Most TNFRSF1A mutations are missense changes and, apart from those affecting conserved cysteines, their deleterious effect remains often questionable. This is especially true for the frequent R92Q mutation, which might not be responsible for TRAPS per se but represents a susceptibility factor to multifactorial inflammatory disorders. This study investigates TRAPS pathophysiology in a family exceptional by its size (13 members) and compares the consequences of several mutations affecting arginine 92.Methods: TNFRSF1A screening was performed by PCR-sequencing. Comparison of the 3-dimensional structure and electrostatic properties of wild-type and mutated TNFR1 proteins was performed by in silico homology modeling. TNFR1 expression was assessed by FACS analysis, western blotting and ELISA in lysates and supernatants of HEK293T cells transiently expressing wild-type and mutated TNFR1.Results: A TNFRSF1A heterozygous missense mutation, R92W (c.361C>T), was shown to perfectly segregate with typical TRAPS manifestations within the family investigated (p |
| Databáze: | OpenAIRE |
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