POS0012 A NEW TNFRSF1A GENE MUTATION IN A TURKISH FAMILY WITH TNF RECEPTOR-ASSOCIATED PERIODIC SYNDROME (TRAPS).

Abstract

BackgroundTumor necrosis factor (TNF) receptor-1 associated periodic syndrome (TRAPS) is a rare autosomal dominant autoinflammatory syndrome caused by pathogenic variants in the tumor necrosis factor receptor 1 (TNFR1) gene (TNF receptor superfamily member 1A, TNFRSF1A). For definitive diagnosis, genetic tests are needed to show variants in the TNFR1 gene (1). Information on genotype-phenotype relationships is limited due to the rarity of the disease.ObjectivesThis study presents novel R97S mutation in TNFRSF1A gene and relevant clinical findings in a patient with amyloidosis of unknown etiology and his sister.MethodsCase; Proband 33-year-old male patient presented with swelling in the legs 9 years ago. In his history, he described muscle pain, unilateral eye redness, swelling and discharge, which occurred several times in 2-3 months and lasted for up to 2 weeks. Kidney biopsy was found to be consistent with AA amylodiosis. FMF (familial Mediterranean fever) gene mutation was detected negative. Colchicine was started at 2x0.5 mg per day.Despite colchicine treatment in the following years, acute phase reactants remained high, proteinuria continued at nephrotic level (5060 mg in 24-hour urine), progressive deterioration of kidney functions, end-stage renal failure developed. Gene analysis was performed for other autoinflammatory diseases; R97S (Nucleotide change c.290_310dup heterozygous) mutation was detected in the TNFRSF1A gene.Sister;31-year-old female patient was admitted to our clinic after a heterozygous mutation in the TNFRSF1A gene was detected in her brother. In her history, she described muscle pain, edema, redness and discharge around the eyes, which occurred 1-2 times a year and lasted for about 2 weeks, especially triggered by the menstrual cycle. TNF (tumor necrosis factor) receptor-associated periodic syndrome mutation was found to be heterozygous positive R97S.Father;The father of the first two cases started having sore throat, diarrhea, muscle pain, swelling around the eyes and fever attacks starting from the age of 29. Renal biopsy revealed apple-green birefringence with congo-red stain, which was indicative of amyloidosis. When he was 32 years old, peritoneal dialysis was started first and then continued with hemodialysis due to end-stage renal disease. Three months after the start of hemodialysis, he died due to high fever, hypotension and septicemia.ResultsIn this article, a novel mutation of TRAPS which has not been reported in the literature so far, is presented in a Turkish family.ConclusionOur patient and her sister with the R97S mutation did not have frequent clinical findings such as febrile serositis attacks and skin rashes. In addition, the incidence of conjunctivitis and periorbital edema in TRAPS cases reported in the literature is between 10-20% (1). Three members of the family presented here had periorbital edema and two had conjunctivitis. It is possible that R97S mutations in the TNFRSF1A gene are associated with the development of periorbital lesions and secondary amyloidosis.Our country is endemic for FMF disease, a study by Bilge et al. (2) demonstrated that mutation analysis of 9% of all subjects with FMF in our country provided negative results. In our opinion genetic analysis should be performed to detect other autoinflammatory diseases in cases that classical FMF attacks are not seen, as in this case series. These and similar cases followed as FMF are likely to be associated with other autoinflammatory diseases. Diagnosing these rare diseases will provide both appropriate and effective treatment options to patients and a better definition of the clinical feature - mutation relationship.