The unsolved mystery of MEFV variants variable expressivity in Familial Mediterranean Fever

Excerpt

Familial Mediterranean Fever (FMF) is the most common and best-known hereditary monogenic recurrent fever syndrome [1]. FMF is an autoinflammatory disorder caused by mutations in the MEFV gene which encodes for the pyrin (marenostrin) protein. Pyrin plays a crucial role in the cell response to several damage- and pathogen-associated molecular patterns (DAMPs and PAMPs, respectively). Via its interaction with the apoptosis-associated speck-like protein containing a CARD (ASC or PYCARD) and procaspase-1, pyrin promotes the release of pro-inflammatory cytokines, namely interleukin (IL)-1b and IL-18 [2]. Although traditionally considered an autosomal recessive disorder, FMF cases associated with a single MEFV mutation or with apparently dominant transmission are increasingly recognized [2‐6]. In addition, FMF shows a strikingly unique prevalence with most patients’ clusters identified in countries bordering the Mediterranean basin, hence its name. Indeed, the FMF prevalence has been calculated as high as 1 in 400/500 in Anatolia and Armenia, 1 in 1000 in the rest of Turkey and in Israel and frequent in other Middle East countries, such as Lebanon, Syria, Jordan, and Iran [7]. In Italy, although no formal epidemiological studies have been performed, FMF has an estimated prevalence ranging from 1/2000 to 1/10000, therefore considered a rare disease (renderPdf.spring (salute.gov.it)). …