MEFV, which codes for pyrin, is a gene of great significance. Pyrin plays a vital role in innate immunity by sensing modifications in Rho GTPase and assembling the pyrin inflammasome, which activates downstream immune responses [4]. Mutations in the MEFV gene are associated with Familial Mediterranean Fever (FMF), an autoinflammatory disease [1,2,3,5,6,7].

FMF is characterized by recurrent attacks of fever, serositis, and erysipelas-like erythema [1]. Although typically considered autosomal recessive, in Middle Eastern countries, a third of patients with FMF manifestations 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]. Pathogenic MEFV gene variants, especially p.Met694Val, increase the risk for Behçet disease (BD) in regions where both FMF and BD are prevalent [2]. Also, MEFV gene mutations may act as disease modifiers in neuro-Behçet's disease and neuro-Sweet disease, and are associated with particular findings and lesion sites in these patients [3]. A novel dominant MEFV p.E583A variant was found in a family, with patients showing a phenotype distinct from classical MEFV mutations, lacking recurrent fever but having recurrent chest and abdominal pain, and the mutation induced pyrin inflammasome assembly and activation [4]. Additionally, MEFV variants in different exons are responsible for various autoinflammatory diseases known as pyrin-associated AIDs or pyrinopathies [5].

In conclusion, the MEFV gene, through its product pyrin, is crucial for innate immunity. Mutations in MEFV are strongly associated with autoinflammatory diseases such as FMF, BD, and others. Understanding the role of MEFV in these disease conditions can potentially provide insights into disease pathogenesis and inform better diagnostic and treatment strategies.

References:

1. Ben-Chetrit, Eldad, Touitou, Isabelle. 2024. The significance of carrying MEFV variants in symptomatic and asymptomatic individuals. In Clinical genetics, 106, 217-223. doi:10.1111/cge.14566. https://pubmed.ncbi.nlm.nih.gov/38818540/

2. Seyahi, Emire, Ugurlu, Serdal, Amikishiyev, Shirkhan, Gul, Ahmet. 2023. Behçet disease, familial Mediterranean fever and MEFV variations: More than just an association. In Clinical immunology (Orlando, Fla.), 251, 109630. doi:10.1016/j.clim.2023.109630. https://pubmed.ncbi.nlm.nih.gov/37216220/

3. Ishikawa, Hidehiro, Shindo, Akihiro, Ii, Yuichiro, Taniguchi, Akira, Tomimoto, Hidekazu. 2019. MEFV gene mutations in neuro-Behçet's disease and neuro-Sweet disease. In Annals of clinical and translational neurology, 6, 2595-2600. doi:10.1002/acn3.50937. https://pubmed.ncbi.nlm.nih.gov/31682063/

4. Wang, Qintao, Jin, Taijie, Jian, Shan, Zhou, Qing, Yu, Xiaomin. 2023. A dominant pathogenic MEFV mutation causes atypical pyrin-associated periodic syndromes. In JCI insight, 8, . doi:10.1172/jci.insight.172975. https://pubmed.ncbi.nlm.nih.gov/37676738/

5. Mertz, Philippe, Boursier, Guilaine, Hentgen, Véronique, Georgin-Lavialle, Sophie. 2024. New Diseases Linked to MEFV Variants or Pyrinopathies. In The journal of allergy and clinical immunology. In practice, 13, 522-532. doi:10.1016/j.jaip.2024.12.022. https://pubmed.ncbi.nlm.nih.gov/39725312/

6. Yamamura, Yuta, Furuichi, Kengo, Toyama, Tadashi, Yachie, Akihiro, Wada, Takashi. 2021. Repeated Necrotizing Lymphadenitis with MEFV Gene Mutations. In Internal medicine (Tokyo, Japan), 61, 1105-1110. doi:10.2169/internalmedicine.7882-21. https://pubmed.ncbi.nlm.nih.gov/34511567/

7. Aksoy, Rahime, Us, Ebru, Aksoy, Darya Farhoomand, Dumlupınar, Ebru, Turgay, Tahsin Murat. 2024. Molecular analyses of MEFV gene mutation variants in Turkish population. In Molecular biology reports, 51, 844. doi:10.1007/s11033-024-09786-x. https://pubmed.ncbi.nlm.nih.gov/39042260/