Τίτλος:
Molecular and clinical spectrum of four pedigrees of TRAPS in Greece: Results from a national referral center
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Objective: Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) is a rare autosomal dominantly inherited autoinflammatory disease caused by mutations of the TNFRSF1A gene. To address the association between TNFRSF1A mutations and clinical phenotype, we analyzed four pedigrees of TRAPS patients. Methods: Four Greek patients with TRAPS-like clinical features were screened for TNFRSF1A mutations by sequencing exons 2, 3 and 4. Following positive testing, twenty-two members of their families were also genetically and clinically screened. Results: Twenty-six members of four unrelated Greek families were investigated. The C73Y (c.305G>A) mutation of the TNFRSF1A gene was identified in five patients, with two of the five carrying a concomitant R92Q variation. We also identified seven C73W (c.306C>G), two T50M (c.236C>T) and seven R92Q (c.362G>A) carriers. Symptoms varied and the C73Y, C73W and T50M mutations were associated with the most severe clinical manifestations. The R92Q phenotype ranged from asymptomatic to mild disease. Molecular modelling linked pathogenicity with aberrant TNFRSF1A disulphide bond formation. Conclusion: In this first pedigree analysis of TRAPS in Greece, we identified the rare C73Y TNFRSF1A mutation. A wide clinical spectrum was observed with the C73Y, C73W and T50M mutations that affect TNFRSF1A disulphide bonds and are associated with worse symptoms. © 2019 The Author(s). Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved.
Συγγραφείς:
Nezos, A.
Argyropoulou, O.D.
Klinaki, E.
Marketos, N.
Karagianni, P.
Eliopoulos, E.
Vlachoyiannopoulos, P.
Maritsi, D.N.
Tzioufas, A.G.
Περιοδικό:
Rheumatology (United Kingdom)
Εκδότης:
Oxford University Press
Λέξεις-κλειδιά:
adalimumab; arginine; canakinumab; colchicine; cysteine; disulfide; glutamine; ibuprofen; methionine; prednisolone; threonine; tnfrsf1a protein; tryptophan; tumor necrosis factor receptor; tyrosine; unclassified drug; tumor necrosis factor receptor 1, adult; amino acid substitution; arthritis; Article; cachexia; case report; child; clinical article; clinical feature; conjunctivitis; disulfide bond; exon; family; female; fever; gene expression; gene identification; gene mutation; genetic association; genetic screening; Greece; heterozygote; human; molecular genetics; molecular model; pathogenicity; patient referral; pedigree; pedigree analysis; phenotype; priority journal; rheumatology; symptom; tumor necrosis factor receptor associated periodic syndrome; uveitis; dna mutational analysis; fever; genetic predisposition; genetics; hereditary periodic fever; male; mutation; phenotype; severity of illness index, DNA Mutational Analysis; Female; Fever; Genetic Predisposition to Disease; Greece; Hereditary Autoinflammatory Diseases; Humans; Male; Models, Molecular; Mutation; Pedigree; Phenotype; Receptors, Tumor Necrosis Factor, Type I; Severity of Illness Index
DOI:
10.1093/rheumatology/kez424
