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

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 penetranc