Clinical significance of P46L and R92Q substitutions in the Tumor Necrosis Factor Superfamily 1A gene

Nathalie Ravet ^1*, Saad Rouaghe ², Catherine Dode ³, Jacques Bienvenu ⁴, Jerome Stirnemann ², Pierre Levy ¹, Marc Delpech ³ and Gilles Grateau ¹

¹ Hôpital Tenon, Assistance publique-Hôpitaux de Paris,(AP-HP), Université Paris 6, France
² Service de médecine interne, Hôpital Jean Verdier, (AP-HP), Université Paris 13, France
³ Hôpital Cochin, (AP-HP), Université Paris 5, France
⁴ Centre hospitalier Lyon-sud, Hospices civils de Lyon, 69495 Pierre-Bénite, France

^* To whom correspondence should be addressed. E-mail: ravetnathalie73{at}yahoo.fr.

Accepted 12 March 2006

Abstract

Objective: TNF Receptor Associated Periodic Syndrome (TRAPS) has been associated with several mutations in TNFReceptor Super Family 1A, including a majority of cysteine substitutions. However, the nature of two substitutions, P46L and R92Q remains a subject of discussion. We aimed to assess the actual role of these two sequence variations in a series of TRAPS patients.

Methods: Main clinical data of eighty nine TRAPS patients have been prospectively registered on a standard form. Eighty four patients or member of families suffering for recurrent episodes of inflammatory symptoms spanning a period of more than 6 months and harbouring a TNFRSF1A mutation were studied. Clinical data have been analysed according the nature of the mutation, P46L, R92Q or other.

Results: P46L is frequent essentially in patients from Maghreb and is associated with a mild phenotype. P46L appears rather as a polymorphism with a non specific role in inflammation. R92Q is associated with a variable phenotype and presents rather as a low penetrance mutation. Interpreting these results needs a confrontation with clinical signs and genetic background.

Keywords: TNFR, TRAPS, genetic polymorphism, penetrance

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