Autoinflammatory syndromes are rare disorders which often have inflammatory features and malfunctions of the innate immune system. It constitutes of a set of disorders with recurrent episodes of inflammation, accompanied by inflammatory cutaneous, mucosal, serosal and osteoarticular manifestations. In general, autoinflammatory syndromes are not caused by infection or innate immune, but are the results of genetically driven dysregulated innate immune response with over-activated inflammasome and cytokines. Affected patients often have first- or second-degree relatives with similar features. Genetic defects have been identified in a range of disorders, including familial Mediterranean fever (FMF), TNF receptor–associated periodic syndrome (TRAPS), hyper-immunoglobulinemia D with periodic fever syndrome (HIDS) and cryopyrin-associated periodic syndromes (CAPS) which include a spectrum of disorders: familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS), neonatal-onset multisystem inflammatory disease (NOMID) and so forth. With advanced understanding of autoinflammatory syndromes, genetic variants will help researchers detect mechanisms of those disorders pre-clinically and clinically.
46 known missense mutations involving TNF receptor type I have been identified to be localized on distal chromosome 12p in patient with TRAPS. Among all the mutations, R92Q and P46L mutations are detected 4% and 1% of the population, respectively. R92Q and T61I polymorphisms are usually related to rheumatoid arthritis and found with an adult onset. The most common autoinflammatory syndromes is FMF, as a result of a recessive mutation of the Mediterranean Fever gene 16p13, located on the short arm of the chromosome 16. Major mutations in FMF have 5 common phenotypes, including M694V, M6941, M680I, V726A and E148Q. Defective function of protein encoded by MEFV and pyrin, results in uncontrolled inflammation with upregulated IFN-γ and circulating proinflammatory cytokines. There are also more gene defects found in different disorders, such as NLRP3 (NOD-like receptor family pyrin domain 3) mutations in CAPS, PSTPIP1 (proline-serine-threonine phosphatase-interacting protein) mutations in PFAPA syndrome, and so on.
To have better understanding of different genetic mutations in various autoinflammatory syndromes, our platform provides targeted DNA sequencing by the Illumina MiSeq or Ion PGM system. You can choose genes from our comprehensive autoinflammatory syndromes panel library for genetic testing or to customize your own panel.
For more information about the Custom Autoinflammatory Syndromes Panel or need other amplification requirements, please contact us.