1. P02-014 - Consequences of Arginine 92 mutations in TNFR1
- Author
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Emmanuelle Cochet, Serge Amselem, Isabelle Jéru, Véronique Hentgen, J Gaillat, Bruno Copin, Serge Charmion, Sonia-Athina Karabina, Philippe Duquesnoy, G Le Borgne, Pascal Cathébras, CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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), Service de Médecine Interne, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Service des Maladies Infectieuses, Centre Hospitalier de la Région d'Annecy (Pringy), Centre de Référence des Maladies AutoInflammatoires, 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), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), CHU Saint-Etienne-Hôpital Nord - Saint-Etienne, and BMC, Ed.
- Subjects
Arginine ,medicine.disease_cause ,Bioinformatics ,03 medical and health sciences ,symbols.namesake ,[SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics ,0302 clinical medicine ,Rheumatology ,medicine ,Immunology and Allergy ,Missense mutation ,Pediatrics, Perinatology, and Child Health ,030212 general & internal medicine ,ComputingMilieux_MISCELLANEOUS ,030203 arthritis & rheumatology ,Genetics ,[SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system ,[SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics ,Mutation ,business.industry ,[SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system ,Periodic syndrome ,Meeting Abstract ,Pediatrics, Perinatology and Child Health ,Mendelian inheritance ,symbols ,business ,Inflammatory disorder - Abstract
International audience; IntroductionTNFRSF1A is involved in a Mendelian autosomal dominant autoinflammatory disorder called TNFR-associatedperiodic syndrome (TRAPS). Most TNFRSF1A mutations are missense changes and, apart from those affectingconserved cysteines, their deleterious effect remains often questionable. This is especially true for the frequentR92Q mutation, which might not be responsible for TRAPS per se but represents a susceptibility factor tomultifactorial inflammatory disorders.ObjectivesThis study investigates TRAPS pathophysiology in a family exceptional by its size (13 members).MethodsTNFRSF1A screening was performed by PCR-sequencing. Comparison of the 3-dimensional structure and electro-static properties of wild-type and mutated TNFR1 proteins was performed by in silico homology modeling. TNFR1expression was assessed by western blotting and ELISA in lysates and supernatants of HEK293T cells transfectedwith plasmids encoding wild-type and mutated TNFR1.ResultsA TNFRSF1A heterozygous missense mutation, R92W(c.361C>T) perfectly segregated with typical TRAPS mani-festations within the family (p
- Published
- 2013