| Autor: |
Isabelle Jéru, Serge Charmion, Emmanuelle Cochet, Bruno Copin, Philippe Duquesnoy, Maria Teresa Mitjavila Garcia, Gaëlle Le Borgne, Pascal Cathebras, Jacques Gaillat, Sonia Karabina, Catherine Dodé, Peter Lohse, Véronique Hentgen, Serge Amselem |
| Jazyk: |
angličtina |
| Rok vydání: |
2013 |
| Předmět: |
|
| Zdroj: |
PLoS ONE, Vol 8, Iss 7, p e69757 (2013) |
| Druh dokumentu: |
article |
| ISSN: |
1932-6203 |
| DOI: |
10.1371/journal.pone.0069757 |
| Popis: |
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: |
Directory of Open Access Journals |
| Externí odkaz: |
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