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.
Ravet
N
N
Service de Médecine Interne, Hôpital Tenon, 4 rue de la Chine, 75970 Paris Cedex 20, Paris, France. nathalie.ravet@tnn.aphp.fr
Rouaghe
S
S
Dodé
C
C
Bienvenu
J
J
Stirnemann
J
J
Lévy
P
P
Delpech
M
M
Grateau
G
G
D000293:Adolescent; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D003078:Colchicine / Q000627:therapeutic use; D010505:Familial Mediterranean Fever / Q000097:blood / Q000188:drug therapy / Q000208:ethnology / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D009154:Mutation; D010641:Phenotype; D011446:Prospective Studies; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics*; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D000894:Anti-Inflammatory Agents, Non-Steroidal; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha; D003078:Colchicine