Muckle-Wells Syndrome

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Muckle-Wells syndrome (MWS) is a rare genetic disorder that causes hive-like skin rashes, chills, fever, partial or total hearing loss, swollen joints, loss of kidney function, and can eventually lead to amyloidosis in some patients. Muckle-Wells syndrome is named after Thomas J. Muckle and Michael V. Wells who first described the disease in April of 1962 [1]. Muckle-Wells is in a family of diseases called Cryopyrin-Associated Autoinflammatory Syndromes (CAPS) which all are related because they are caused by a deficiency in the NLRP3 gene which is what codes for the protein Cryopyrin [2,3]. People tend to start showing symptoms as early as infancy or early childhood, and affects them for their entire lives, and if not treated can cause death …show more content…
Muckle-Wells syndrome is primarily caused by a mutation on the NLRP3 (also called CIAS1) gene which is responsible for coding for the protein Cryopyrin. Cryopyrin is a type of protein which is called a nucleotide-binding domain and leucine-rich repeat containing protein. A major part of the innate immune system is the inflammasome, which Cryopyrin is directly involved in the correct assembly of this molecule [6]. An inflammasome is the molecule that directs the process of inflammation in the body. Inflammation is the body’s way of signaling to leukocytes and other signal molecules to rush to the site of injury or disease to begin fighting it to prevent it from damaging tissue. The leukocytes fight whatever pathogens are present and the signaling molecules initiate the process of tissue repair. After this is complete, the body inhibits the inflammatory response to prevent it from …show more content…
The NLRP3 gene is located on Chromosome one in the 1q44 position [14]. Approximately one hundred different mutations have been found to cause this problem with the NLRP gene [15]. Almost all of the mutations are located on exon 3, which begins before the start codon but goes several hundred base pairs into the coding DNA sequence (Figure 2). Most of the mutations that cause this deficiency as caused by a type of mutation referred to as a missense mutation. This type of mutation is caused by a point mutation, or when a single base pair is changed to another, this change then alters the codon which changes the amino acid in the peptide chain. This usually results in a protein that is defective, or loses the ability to fold in such a way that allows it to function properly. Sometimes a point mutation can code for a premature stop codon, and depending on where it is in the normal sequence of amino acids, it can severely alter the protein produced [16]. One mutation that has been shown to cause this defect on the NLRP3 gene is the p.D303N mutation. This mutation causes a G907A (Guanine to Adenine) transition on the DNA. This point mutation changes only one amino acid aspartic acid into asparagine in the peptide chain [17]. This is the most common mutation that causes

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