Based on the pathophysiology in FMF described above, pyrin mutations, particularly in exon 10 (forms the B30.2 domain, a site that interacts with caspase-1), are thought to hamper pyrin phosphorylation and are thereby prone to activate pyrin and cause intermittent and often chronic systemic and local inflammation, manifested with the FMF phenotype [20,27]. The gene discussed is CASP1; the disease is familial Mediterranean fever.