Mefv-flox Mouse

MEFV, which codes for pyrin, is a crucial gene involved in the innate immune response. Pyrin can sense modifications in Rho GTPase and assemble the pyrin inflammasome, activating downstream immune responses [4]. The gene is associated with various autoinflammatory diseases [1,2,3,5,6].

Familial Mediterranean fever (FMF), an autosomal recessive autoinflammatory disease, is strongly associated with MEFV gene variants, especially in exon 10 [1,5,7]. However, in Middle Eastern countries, a third of FMF-expressing patients carry a single mutation, and some cases of pure dominant inheritance linked to specific single MEFV variants have been reported, complicating genetic testing interpretation [1]. Additionally, MEFV gene mutations may act as disease modifiers in neuro-Behçet's disease and neuro-Sweet disease, with mutations frequently observed (70.6%) and associated with certain clinical features like headaches, exertional leg pain, and specific lesion sites [3]. A novel dominant MEFV p.E583A variant was identified in a family, causing an atypical pyrin-associated periodic syndrome without recurrent fever but with recurrent chest and abdominal pain, and colchicine effectively controlled the phenotype [4]. Also, different exons of MEFV are associated with various autoinflammatory diseases known as pyrinopathies [5].

In conclusion, MEFV is essential for the innate immune response through pyrin-mediated inflammasome activation. Studies on MEFV-associated genetic variants have provided insights into the pathogenesis of autoinflammatory diseases such as FMF, as well as other related disorders like neuro-Behçet's disease, neuro-Sweet disease, and pyrinopathies. Understanding MEFV's role helps in better diagnosis, interpretation of genetic testing, and potentially developing more targeted treatment strategies for these diseases.