A novel TNFRSF1 gene mutation in a Turkish family: a report of three cases

Abstract

Tumor necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS) is an autosomal dominantly inherited rare autoinflammatory disease. It is caused by mutations in exons 2-3 and 4-5 of the tumor necrosing factor receptor superfamily 1A (TNFRSF1A) gene on chromosome 12p13.2. TNFRSF1A gene encodes the 55-kDa receptor for tumor necrosis factor. Attacks are associated with abdominal pain, myalgia, erythematous skin rash, conjunctivitis, and periorbital edema. Until now, more than 80 mutations have been identified. We herein report three patients with TRAPS of Turkish origin. The patients were followed up in our outpatient clinic in Kocaeli University Division of Rheumatology. Because of their TRAPS associated clinical features, we isolated genomic DNA from whole blood and sequenced the exon 2-3 and 4-5 third exon of TNFRSF1A gene after amplification with appropriate primers. One of the patients with TRAPS was 47-year-old female, who described recurrent attacks of fever, urticarial rash, conjunctivitis, arthralgia, myalgia, abdominal pain, thoracic pain, headache, fatigue, and elevated acute phase response since her childhood. With the sequencing of the TNFRSF1A gene, we identified heterozygous C29R mutation, which has not been reported before in any TRAPS patient. The other patients are her sons with similar findings and age 29 and 26. They were heterozygous for C29R mutation in TNFRSF1A gene too. We report novel C29R mutation in three TRAPS patients of Turkish origin, in which the main clinical features are recurrent fever attacks, erythematous skin rash, conjunctivitis, myalgia, and arthralgia. Treatment with steroids resolved the symptoms and lesions.