We sequenced DNA from members of this family to determine whether the TNFAIP3 frameshift mutation and/or MEFV variants could explain this autoinflammatory disease pedigree.
The pyrin inflammasome also plays a role in mediating inflammation in other autoinflammatory diseases linked to dysregulation in the actin polymerization pathway.
Mutations in the MEFV gene have been linked to autoinflammatory diseases such as familial Mediterranean fever (FMF) or pyrin-associated autoinflammation with neutrophilic dermatosis (PAAND).
In countries where FMF and other autoinflammatory diseases are prevelant, systemic amyloidosis should be kept in mind in the differential diagnosis of children who present with nephrotic syndrome and abdominal mass.
Familial Mediterranean fever (FMF) is an IL-1β-dependent autoinflammatory disease caused by mutations of Mediterranean fever (MEFV) encoding pyrin and characterized by inflammatory attacks induced by physical or psychological stress.
Originally identified in plants, evidence that a similar guardlike mechanism exists in humans has recently been identified, whereby a mutation that prevents phosphorylation of the innate immune sensor pyrin triggers a dominantly inherited autoinflammatory disease.
Mutations in the B30.2/SPRY domain cause pathogen-independent activation of pyrin and are responsible for the autoinflammatory disease familial Mediterranean fever (FMF).
Thus, our data provide evidence for an ASC-dependent NLRP3-independent inflammasome in which gain-of-function pyrin mutations cause autoinflammatory disease.
During the last decade, the increasing knowledge on the pathogenic mechanisms related to a number of diseases associated to mutations of genes associated to autoinflammatory diseases had a terrific impact on the understanding of pivotal mechanisms regulating the inflammatory response and therefore represents one of the major advance in the field of inflammation.The International Congress on Familiar Mediterranean Fever and Systemic Autoinflammatory Diseases brings together the experts in the field every two and a half years and represents a unique opportunity for an update on the recent progress in this growing field.
Autoinflammatory diseases constitute a large spectrum of monogenic diseases like FMF or cryopyrin-associated periodic syndromes (CAPS) and complex genetic trait diseases such as systemic onset juvenile idiopathic arthritis (SoJIA).
Changing our concept regarding the MEFV gene and its link to such clinical phenotypes may call for a higher awareness of the existence of additional autoinflammatory diseases.
On the other hand, asthma is less frequent in individuals with familial Mediterranean fever, an autoinflammatory disease prevalent in the Iraqi Jewish community and linked to mutations in the familial Mediterranean fever gene, designated MEFV.
De novo CIAS1 mutations, cytokine activation, and evidence for genetic heterogeneity in patients with neonatal-onset multisystem inflammatory disease (NOMID): a new member of the expanding family of pyrin-associated autoinflammatory diseases.