Musckle-Wells syndrome ... (Muckle-Wells syndrome) - Gen NLRP3 (CIAS1).

The Muckle-Wells syndrome is a disorder characterized by periodic episodes of rash, fever, joint pain, progressive hearing loss and kidney damage.

Affected individuals have recurring episodes that begin in infancy or early childhood. These episodes can occur spontaneously or be triggered by cold, heat, fatigue, or other stresses. People usually develop a non - itchy rash, mild to moderate fever, painful and swollen joints, and sometimes conjunctivitis. The progressive nerve damage leads to sensorineural hearing loss that becomes evident during adolescence. About a third of people with Muckle-Wells syndrome have progressive kidney damage caused by amyloidosis, may also damage other organs.

This process is due to mutations in the gene NLRP3, located on the long arm of chromosome 1 (1q44), also known as CIAS1. This gene encodes cryopyrin protein. This protein belongs to a family of proteins called nucleotide binding domain and leucine rich repeats that are located within the cytoplasm. These proteins are involved in the immune system, helping to regulate the process of inflammation. Inflammation occurs when the immune system sends signaling molecules and white blood cells are attracted to the site of injury or disease to combat microbial invaders and facilitate tissue repair. When this has been accomplished, the body inhibits the inflammatory response to prevent damage to its own cells and tissues. Cryopyrin protein is involved in the assembly of a molecular complex called inflammasome, which helps stimulate the inflammatory process.

They have identified at least 10 mutations in exon 3 of the gene that cause NLRP3 Muckle-Wells syndrome. It is believed that mutations in the gene give rise to an overactive cryopyrin protein and an inappropriate inflammatory response, causing episodes of fever and damage to body cells and tissues.

This disease is usually inherited as an autosomal dominant, which means that a copy of the altered gene in each cell is sufficient to cause the disorder. In some cases, the pattern of inheritance is unknown.  

Tests in IVAMI: in IVAMI perform detection of mutations associated with Muckle-Wells syndrome, by complete PCR amplification of exons NLRP3 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).