Phenotypic characterization of Familial Mediterranean Fever patients harboring variants of uncertain significance

Background/aim: Familial Mediterranean Fever (FMF) is the prototype of hereditary autoinflammatory disorders and caused by mutations on the MEFV gene located on the short arm of chromosome 16. Although some MEFV variants are clearly associated with disease phenotype, there are numerous variants with unknown clinical association which are termed as variants of uncertain significance (VUS). Here, we present clinical correlations of VUS in a large cohort of adult FMF patients from three tertiary centers located in Central Anatolia. Materials and methods: All patients were recruited from FMF in Central Anatolia (FiCA) cohort. Demographic (sex, age at disease onset) and clinical features (disease characteristics, attack frequency, mean colchicine dose, colchicine nonresponsiveness, amyloidosis, and persistent inflammation) of patients with VUS were compared with those harboring pathogenic variants. Disease severity and damage were also evaluated using international severity score for FMF (ISSF) and autoinflammatory disease damage index (ADDI), respectively. Results: Among 971 participants included, MEFV gene analysis results were available for 814 patients. Twenty-six (3.2%) patients had single heterozygous VUS and 54 (6.6%) had pathogenic/VUS complex heterozygous variants. Patients with single heterozygous VUS had similar demographic/clinical features, ISSF and ADDI scores compared to those with single heterozygous pathogenic variant (p > 0.05 for all). No difference was observed in the demographic and clinical features of patients with single heterozygous pathogenic mutation and pathogenic/VUS complex heterozygous variant (p > 0.05 for all). ISSF and ADDI scores were lower in pathogenic/VUS complex heterozygous patients than those harboring single pathogenic mutation (p = 0.006 and 0.004, respectively). Conclusion: Our findings suggest that patients with single heterozygous VUS has mild FMF phenotype similar to those with single pathogenic mutation. Pathogenic/VUS complex heterozygosity does not lead to a more severe clinical phenotype than having a single pathogenic variant.Key words: Familial Mediterranean Fever, MEFV, variants of uncertain significance, genetics, phenotype

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APA	SARI A, BODAKÇİ E, ARMAĞAN B, Satış H, Atas N, BİLGE N, Bilici Salman R, Yardimci G, Babaoglu H, Kılıç L, öztürk m, HAZNEDAROGLU S, GÖKER B, Kalyoncu U, KASIFOGLU T, TUFAN A (2021). Phenotypic characterization of Familial Mediterranean Fever patients harboring variants of uncertain significance. , 1695 - 1701. 10.3906/sag-2011-273
Chicago	SARI ALPER,BODAKÇİ ERDAL,ARMAĞAN Berkan,Satış Hasan,Atas Nuh,BİLGE Nazife Sule YAŞAR,Bilici Salman Reyhan,Yardimci Gozde Kubra,Babaoglu Hakan,Kılıç Levent,öztürk mehmet akif,HAZNEDAROGLU SEMINUR,GÖKER Berna,Kalyoncu Umut,KASIFOGLU TIMUCIN,TUFAN ABDURRAHMAN Phenotypic characterization of Familial Mediterranean Fever patients harboring variants of uncertain significance. (2021): 1695 - 1701. 10.3906/sag-2011-273
MLA	SARI ALPER,BODAKÇİ ERDAL,ARMAĞAN Berkan,Satış Hasan,Atas Nuh,BİLGE Nazife Sule YAŞAR,Bilici Salman Reyhan,Yardimci Gozde Kubra,Babaoglu Hakan,Kılıç Levent,öztürk mehmet akif,HAZNEDAROGLU SEMINUR,GÖKER Berna,Kalyoncu Umut,KASIFOGLU TIMUCIN,TUFAN ABDURRAHMAN Phenotypic characterization of Familial Mediterranean Fever patients harboring variants of uncertain significance. , 2021, ss.1695 - 1701. 10.3906/sag-2011-273
AMA	SARI A,BODAKÇİ E,ARMAĞAN B,Satış H,Atas N,BİLGE N,Bilici Salman R,Yardimci G,Babaoglu H,Kılıç L,öztürk m,HAZNEDAROGLU S,GÖKER B,Kalyoncu U,KASIFOGLU T,TUFAN A Phenotypic characterization of Familial Mediterranean Fever patients harboring variants of uncertain significance. . 2021; 1695 - 1701. 10.3906/sag-2011-273
Vancouver	SARI A,BODAKÇİ E,ARMAĞAN B,Satış H,Atas N,BİLGE N,Bilici Salman R,Yardimci G,Babaoglu H,Kılıç L,öztürk m,HAZNEDAROGLU S,GÖKER B,Kalyoncu U,KASIFOGLU T,TUFAN A Phenotypic characterization of Familial Mediterranean Fever patients harboring variants of uncertain significance. . 2021; 1695 - 1701. 10.3906/sag-2011-273
IEEE	SARI A,BODAKÇİ E,ARMAĞAN B,Satış H,Atas N,BİLGE N,Bilici Salman R,Yardimci G,Babaoglu H,Kılıç L,öztürk m,HAZNEDAROGLU S,GÖKER B,Kalyoncu U,KASIFOGLU T,TUFAN A "Phenotypic characterization of Familial Mediterranean Fever patients harboring variants of uncertain significance." , ss.1695 - 1701, 2021. 10.3906/sag-2011-273
ISNAD	SARI, ALPER vd. "Phenotypic characterization of Familial Mediterranean Fever patients harboring variants of uncertain significance". (2021), 1695-1701. https://doi.org/10.3906/sag-2011-273

APA	SARI A, BODAKÇİ E, ARMAĞAN B, Satış H, Atas N, BİLGE N, Bilici Salman R, Yardimci G, Babaoglu H, Kılıç L, öztürk m, HAZNEDAROGLU S, GÖKER B, Kalyoncu U, KASIFOGLU T, TUFAN A (2021). Phenotypic characterization of Familial Mediterranean Fever patients harboring variants of uncertain significance. Turkish Journal of Medical Sciences, 51(4), 1695 - 1701. 10.3906/sag-2011-273
Chicago	SARI ALPER,BODAKÇİ ERDAL,ARMAĞAN Berkan,Satış Hasan,Atas Nuh,BİLGE Nazife Sule YAŞAR,Bilici Salman Reyhan,Yardimci Gozde Kubra,Babaoglu Hakan,Kılıç Levent,öztürk mehmet akif,HAZNEDAROGLU SEMINUR,GÖKER Berna,Kalyoncu Umut,KASIFOGLU TIMUCIN,TUFAN ABDURRAHMAN Phenotypic characterization of Familial Mediterranean Fever patients harboring variants of uncertain significance. Turkish Journal of Medical Sciences 51, no.4 (2021): 1695 - 1701. 10.3906/sag-2011-273
MLA	SARI ALPER,BODAKÇİ ERDAL,ARMAĞAN Berkan,Satış Hasan,Atas Nuh,BİLGE Nazife Sule YAŞAR,Bilici Salman Reyhan,Yardimci Gozde Kubra,Babaoglu Hakan,Kılıç Levent,öztürk mehmet akif,HAZNEDAROGLU SEMINUR,GÖKER Berna,Kalyoncu Umut,KASIFOGLU TIMUCIN,TUFAN ABDURRAHMAN Phenotypic characterization of Familial Mediterranean Fever patients harboring variants of uncertain significance. Turkish Journal of Medical Sciences, vol.51, no.4, 2021, ss.1695 - 1701. 10.3906/sag-2011-273
AMA	SARI A,BODAKÇİ E,ARMAĞAN B,Satış H,Atas N,BİLGE N,Bilici Salman R,Yardimci G,Babaoglu H,Kılıç L,öztürk m,HAZNEDAROGLU S,GÖKER B,Kalyoncu U,KASIFOGLU T,TUFAN A Phenotypic characterization of Familial Mediterranean Fever patients harboring variants of uncertain significance. Turkish Journal of Medical Sciences. 2021; 51(4): 1695 - 1701. 10.3906/sag-2011-273
Vancouver	SARI A,BODAKÇİ E,ARMAĞAN B,Satış H,Atas N,BİLGE N,Bilici Salman R,Yardimci G,Babaoglu H,Kılıç L,öztürk m,HAZNEDAROGLU S,GÖKER B,Kalyoncu U,KASIFOGLU T,TUFAN A Phenotypic characterization of Familial Mediterranean Fever patients harboring variants of uncertain significance. Turkish Journal of Medical Sciences. 2021; 51(4): 1695 - 1701. 10.3906/sag-2011-273
IEEE	SARI A,BODAKÇİ E,ARMAĞAN B,Satış H,Atas N,BİLGE N,Bilici Salman R,Yardimci G,Babaoglu H,Kılıç L,öztürk m,HAZNEDAROGLU S,GÖKER B,Kalyoncu U,KASIFOGLU T,TUFAN A "Phenotypic characterization of Familial Mediterranean Fever patients harboring variants of uncertain significance." Turkish Journal of Medical Sciences, 51, ss.1695 - 1701, 2021. 10.3906/sag-2011-273
ISNAD	SARI, ALPER vd. "Phenotypic characterization of Familial Mediterranean Fever patients harboring variants of uncertain significance". Turkish Journal of Medical Sciences 51/4 (2021), 1695-1701. https://doi.org/10.3906/sag-2011-273