Receptor tumor necrosis factor, associated periodic syndrome ... (Tumor necrosis factor receptor-associated periodic syndrome -TRAPS-) - Gen TNFRSF1A
The associated periodic syndrome receptor tumor necrosis factor (TRAPS) is a disorder characterized by recurrent episodes of fever. In general, these febrile episodes usually last about 3 weeks but can last from a few days to several months. The frequency of episodes varies greatly among affected individuals, may occur every 6 weeks or even every few years. Typically, episodes of fever occur spontaneously, but can sometimes be caused by a variety of triggers such as minor injuries, infections, stress, exercise, or hormonal changes.
During episodes of fever, people may show additional signs and symptoms such as abdominal and muscle pain, rash, periorbital edema, joint pain, and inflammation in various areas of the body including the eyes, heart muscle, certain joints, throat or mucous membranes and the digestive tract. Between 15% and 20% of those affected by the disease develop amyloidosis, abnormal accumulation of a protein called amyloid in kidneys which can lead to renal failure.
The associated periodic syndrome receptor tumor necrosis factor is due to mutations in the gene TNFRSF1A (Tumor necrosis factor receptor superfamily member 1A), located on the short arm of chromosome 12 (12p13.2). This gene encodes a protein called receptor 1 tumor necrosis factor (TNFR1). This protein is found in the cell membrane, where it binds to another protein called tumor necrosis factor (TNF). This connection, sends signals that can cause the cell initiates inflammation or destruction. Signaling within the cell initiates a route that becomes a protein called nuclear factor kappa B causing inflammation and cytokine synthesis. Apoptosis is initiated when TNFR1 protein, protein bound to TNF, is located in the cell and triggers a process known as caspase cascade.
They have identified 60 mutations in the gene TNFRSF1A, causing the associated periodic syndrome receptor tumor necrosis factor. Most of these mutations change amino acids in protein, which often involve the amino acid cysteine. Cysteines containing sulfur atoms that form disulphide bonds with other cysteines. Disulfide bonds to help protein fold by connecting cysteines in different regions of the protein, giving the appropriate shape to perform its particular function. When cysteines within TNFR1 protein are replaced with other amino acids, the disulfide bonds are not formed, and the protein folds bad. These misfolded proteins are trapped inside the cell and are not able to reach the cell surface to interact with TNF. It is believed that within the cell, these proteins are clustered and alternative pathways trigger initiate inflammation. Protein aggregates constantly activate these alternative pathways of inflammation, leading to excessive inflammation in people with the disease. Moreover, since only one copy of TNFRSF1A gene has a mutation, some proteins normal TNFR1 occur and can bind to the TNF protein, leading to further inflammation. It is unclear whether the disruption of apoptosis pathway plays a role in the signs and symptoms of the disease.
Some people with mutations in the gene do not develop TNFRSF1A TRAPS, or show very mild disease characteristics. Although the reason for this variability is unclear, it is believed that other factors, such as additional genetic changes or environmental factors may play a role in the development of receptor - associated periodic syndrome tumor necrosis factor.
This disease is inherited as an autosomal dominant, which means that a copy of the altered gene in each cell is sufficient to cause the alteration. However, some people who inherit the altered gene never develop disease characteristics. This situation is known as reduced penetrance. It is not clear why some people with a mutated gene develop the disease and others with the mutated gene do not. In most cases, an affected person inherits the mutation from an affected parent. Other cases are caused by new mutations in the gene and occur in people with no history of disease in your family.
Tests in IVAMI: in IVAMI perform detection of mutations associated with associated periodic syndrome receptor tumor necrosis factor (TRAPS), by complete PCR amplification of exons TNFRSF1A gene, and subsequent sequencing.
Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).