TNFRSF1A MUTATIONS IN ITALIAN PATIENTS AFFECTED BY APPARENTLY SPORADIC PERIODIC FEVER SYNDROME

摘要

Hereditary periodic fevers are autoinflammatory disorders characterized by recurrent febrile episodes with serositis, synovitis and cutaneous inflammation, potentially leading to development of AA amyloidosis (1). Genetic testing has greatly improved their diagnosis and treatment, particularly in patients without typical ethnic background. Familial Mediterranean fever (FMF), caused by mutations in MEFV, is the more prevalent and best-characterised hereditary periodic fever in Italy. However, occurrence of other hereditary fever syndromes has not been assessed. The Tumor Necrosis Factor (TNF) receptor-associated periodic syndrome (TRAPS) is a genetically distinct disorder mainly affecting people of Northern European origin. This dominantly inherited syndrome is caused by mutations in. the TNFRSF1A gene, which codifies for the p55 subunit of the TNF receptor. Typical features include localized myalgia, periorbita! edema, conjunctivitis and long duration of attacks, usually lasting more than one week. To date, 24 different mutations have been identified, all clustering in the first and second extracellular cysteine rich domains (CDRs) of this receptor (2). We searched for mutations in MEFV and TNFRSF1A in 48 Italian patients with unexplained, recurrent fever not fulfilling the diagnostic criteria for familial Mediterranean fever. None of these patients had a significant family history for the disease.