Familial Mediterranean fever: New phenotypes and genetic mechanisms

. - Familial Mediterranean fever (FMF, OMIM #249100) is the prototype of a group of inherited diseases of innate immunity known as auto -inflammatory diseases. Its name sums up the main characteristics of the disease. It is an inflammatory disease, which mainly occurs in populations of Mediterranean origin and whose main symptom is recurrent fever. Its classic mode of inheritance is autosomal recessive. The MEditerranean FeVer (MEFV) gene encodes pyrin, a component of the inflammasome of the same name, which is constitutionally activated by pathogenic mutations. The main mutations responsible for FMF are located in exon 10. Thanks to new sequencing approaches, nearly 400 sequence variants are now reported in an online database (Infevers) dedicated to auto -inflammatory diseases, and new molecular mechanisms such as duplication and mosaicism have been identified. The range of phenotypes linked to MEFV has also widened considerably. Mutations in exon 8 are responsible for clinically and genetically atypical auto -inflammatory syndromes (dominant transmission in non -Mediterranean patients). Mutations located in or close to codon 242 of exon 2 are responsible for a rare dermatological disease called pyrin-associated auto -inflammation with neutrophilic dermatosis (PAAND) that is clinically very different from FMF. All the phenotypes associated with the MEFV gene are grouped under the generic term pyrin-associated auto -inflammatory diseases (PAAD). This review summarises recent advances on the new phenotypes and genetic mechanisms linked to the FMF gene. (c) 2023 l'Academie nationale de medecine. Published by Elsevier Masson SAS. All rights reserved.