A novel tumour necrosis factor receptor mutation in a Finnish family with periodic fever syndrome

• Published in: Scandinavian journal of rheumatology 2004-05, Vol.33 (3), p.140-144
• Main Authors: Stjernberg-Salmela, S, Pettersson, T, Karenko, L, Blazevic, V, Nevala, H, Pitkänen, S, Peterson, P, Ranki, A
• Format: Article
• Language: English
• Subjects: Adult; autoinflammatory syndrome; Biological and medical sciences; Diseases of the osteoarticular system; DNA Mutational Analysis; Enzyme-Linked Immunosorbent Assay; Female; Fever - genetics; Fever - immunology; Finland; Humans; Medical sciences; Mutation, Missense; Pedigree; Periodicity; Polymerase Chain Reaction; Receptors, Tumor Necrosis Factor - genetics; Syndrome; TNF receptor; TRAPS
• ISSN: 0300-9742; 1502-7732
• DOI: 10.1080/03009740310004892

Objective: To report a novel mutation of the TNF receptor type 1 gene (TNFRSF1A) in a Finnish patient and her mother, both suffering from periodic fever. Methods: Soluble TNFRSF1A in serum was measured by enzyme-linked immunoabsorbancy, and induced TNFRSF1A shedding from monocyte cell surfaces was determined using fluorescence-activated cell sorter. Mutation detection was performed using PCR amplification and sequencing of the ten exons of TNFRSF1A. Results: Low levels of soluble TNFRSF1A were detected in both patients between attacks. Sequencing revealed a missense mutation in exon 3 in the second extracellular domain of TNFRSF1A, resulting in a substitution of cysteine with arginine at residue 73 (C73R), confirming the diagnosis of TNF receptor-associated periodic syndrome (TRAPS). We were unable to demonstrate a distinct TNFRSF1A shedding defect. Conclusion: In patients of Nordic descent, affected by dominantly inherited recurrent fever, TRAPS is a diagnosis worthy of attention. All TNFRSF1A mutations hitherto described in the Nordic countries have been different.