Missense mutation V20A in the tumor necrosis factor receptor superfamily 1A (TNFRSF1A) gene is associated with tumor necrosis factor receptor-associated periodic syndrome (TRAPS) presenting with periodic gastrointestinal symptoms

2011 ◽  
Vol 17 (6) ◽  
pp. 1445-1446 ◽  
Author(s):  
Qingping Yao ◽  
Lisa Yerian ◽  
Bo Shen
Keyword(s):  
Tumor Necrosis Factor ◽  
Missense Mutation ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Receptor ◽  
Gastrointestinal Symptoms ◽  
Periodic Syndrome ◽  
Tnfrsf1a Gene ◽  
Necrosis Factor

Typical and severe tumor necrosis factor receptor–associated periodic syndrome in the absence of mutations in the TNFRSF1A gene: a case series

2010 ◽  
Vol 32 (12) ◽  
pp. 4015-4018 ◽  
Author(s):  
Luca Cantarini ◽  
Orso Maria Lucherini ◽  
Rolando Cimaz ◽  
Donato Rigante ◽  
Cosima Tatiana Baldari ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Receptor ◽  
Case Series ◽  
Periodic Syndrome ◽  
Tnfrsf1a Gene ◽  
Necrosis Factor

scholarly journals Revisiting TNF Receptor-Associated Periodic Syndrome (TRAPS): Current Perspectives

2020 ◽  
Vol 21 (9) ◽  
pp. 3263 ◽  
Author(s):  
Cornelia Cudrici ◽  
Natalie Deuitch ◽  
Ivona Aksentijevich
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Inflammatory Responses ◽  
Treatment Options ◽  
Tumor Necrosis Factor Receptor ◽  
Periodic Syndrome ◽  
Pathogenic Variants ◽  
Tnfrsf1a Gene ◽  
Receptor Shedding ◽  
Necrosis Factor

Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) is an autosomal dominant autoinflammatory syndrome characterized by prolonged and recurrent episodes of fever, abdominal and/or chest pain, arthralgia, myalgia, and erythematous rash. TRAPS is associated with heterozygous variants in the TNFRSF1A gene, which encodes the TNFR1 (tumor necrosis factor receptor 1) receptor. Disease-causing variants are found exclusively in the extracellular domain of TNFR1 and affect receptor structure and binding to the TNF ligand. The precise mechanism of the disease is still unclear, but it is thought that intracellular accumulation of misfolded mutant protein leads to endoplasmic reticulum stress and enhanced inflammatory responses through constitutive activation of various immune pathways. Other possible mechanisms contributing to the disease pathogenesis include defective receptor shedding, TNF-induced cell death, production of reactive oxygen species, and autophagy impairment. Patients’ leucocytes are hyperresponsive to stimulation and produce elevated levels of proinflammatory cytokines. Systemic autoimmune (AA) amyloidosis is an important cause of morbidity and mortality in TRAPS. Over the last two decades, new therapies have changed the progression and outcome of the disease. In this review, we summarize clinical data from 209 patients with validated pathogenic variants reported in the literature and discuss TRAPS diagnosis, pathogenesis, and treatment options.

scholarly journals Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS) with a New Pathogenic Variant in TNFRSF1A Gene in a Family of the Adult Male with Renal AA Amyloidosis—Diagnostic and Therapeutic Challenge for Clinicians

2021 ◽  
Vol 10 (3) ◽  
pp. 465
Author(s):  
Jolanta Zegarska ◽  
Ewa Wiesik-Szewczyk ◽  
Ewa Hryniewiecka ◽  
Beata Wolska-Kusnierz ◽  
Dariusz Soldacki ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Structural Changes ◽  
Clinical Symptoms ◽  
Tumor Necrosis Factor Receptor ◽  
Three Dimensional ◽  
Periodic Syndrome ◽  
Aa Amyloidosis ◽  
Tnfrsf1a Gene ◽  
Necrosis Factor

Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) belongs to systemic autoinflammatory diseases (AIDs). Many of these syndromes are genetically conditioned and can be inherited. Diagnosis relies on clinical symptoms and should be confirmed by genetic testing. One of the most serious complications is AA amyloidosis. We present the diagnostic route of a 33-year-old male with AA amyloidosis and his children, leading to diagnosis of monogenic autoinflammatory syndrome, confirmed by genetic analysis. A novel variant of the in-frame insertion type in one allele of TNFRSF1A gene was found by whole exome sequencing and confirmed by Sanger sequencing, which allowed a diagnosis of TRAPS. Three-dimensional modeling was used to assess the structural changes introduced into TNFR1 molecule by the insertion. The analysis of the 3D model revealed that accommodation of the 4AA insert induces misalignment of three cysteine bridges (especially the C70-C96 bridge) in the extracellular domain, leading to putatively misfolded and improperly functioning TNFR1. Three of the patient’s daughters inherited the same variant of the TNFRSF1A gene and presented TRAPS symptoms. TRAPS is a very rare disease, but in the presence of suggestive symptoms the genetic diagnostic workout should be undertaken. Early diagnosis followed by appropriate clinical management can prevent irreversible complications.

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