Investigation the importance of TNFRSF1A gene variants in periodic fever syndromes

?Tumour Necrosis Factor Receptor Associated Periodic Syndrome? was reported for the first time as ?Familial Hibernian Fever? in Irish/Scottish family by Williamson and his collaborators in 1982. The gene responsible for the syndrome was defined in 1998 as Tumour Necrosis Factor Receptor Super Family 1A (TNFRSF1A) which is located in the short arm of chromosome 12, and later the syndrome was identified as TNF Receptor Associated Periodic Syndrome (TRAPS). The syndrome was reported mainly in European countries as well as other countries such as India, Turkey, Japan, Israel and exhibits a broad ethnic diversity.There have been 98 different variants of TNFRSF1A identified so far, and 65 of which were reported to cause TRAPS phenotype.Our aim was to evaluate the distribution and frequency of TNFRSF1A gene variants in cases with periodic fever syndrome symptoms. The DNA sequence analysis for all exons of TNFRSF1A gene was performed for 30 cases. None of the mutations that was reported as TRAPS causing before, was identified in our study. However a synonym c.36 A>G transition in exon 1 in 18 cases (G allel frequency %40, A allel frequency %60), c.473?33 T>C transition in intron 4 in 27 cases (T allel frequency %28, C allel frequency %72), c.625+10 A>G transition in intron 6 in 18 cases (A allel frequency %62, G allel frequency %38), c.740?9 T>C transition in intron 7 in 16 cases (C allel frequency %30, T allel frequency %70) and a novel transversion c.626?32 G>T in intron 6 in 1 case were detected.Our study is important for being, in our country, the first study in which the importance of TNFRSF1A gene variants in clinical manifestations of TRAPS in a large patient group was investigated. Keywords: DNA sequencing analysis, Periodic fever syndrome, TRAPS, TNFRSF1A.