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Clinical significance of P46L and R92Q substitutions in the tumour necrosis factor superfamily 1A gene


Objective: Tumour necrosis factor receptor-associated periodic syndrome (TRAPS) has been associated with several mutations in the TNF receptor super family 1A (TNFRSF1A), including most cysteine substitutions. However, the nature of two substitutions, P46L and R92Q, remains a topic of discussion. The aim of this study was to assess the actual role of these two sequence variations in a series of patients with TRAPS.

Methods: The main clinical data of 89 patients with TRAPS have been prospectively registered on a standard form. 84 patients or members of families with 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 to the nature of the mutation—P46L, R92Q or others.

Results: P46L is often seen in patients from Maghreb and is associated with a mild phenotype. P46L appears as a polymorphism with a non-specific role in inflammation. R92Q is associated with a variable phenotype and presents as a low-penetrance mutation. Interpreting these results will require a comparison with clinical signs and genetic background.

  • CRD, cysteine-rich domain
  • FMF, familial Mediterranean fever
  • TNF, tumour necrosis factor
  • TNFRSF, TNF receptor super family
  • TRAPS, TNF receptor-associated periodic syndrome

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