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- ASC, apoptosis associated speck-like protein containing a caspase recruitment domain
- BSA, bovine serum albumin
- DAPI, 4′,6′-diamidino-2-phenylindole
- FMF, familial Mediterranean fever
- M/P, marenostrin/pyrin
- NGS, normal goat serum
Familial Mediterranean fever (FMF) is an autosomal recessive disorder characterised by recurrent episodes of fever and serosal inflammation, which is common in Armenian, Turkish, Arab, and Sephardic Jewish populations. For many years, its diagnosis was one of exclusion, based solely on clinical criteria. However, this difficult situation was changed in 1997 by the identification of the causative gene, MEFV, a discovery that has opened the possibility of facilitating the diagnosis of this disease. Indeed, as shown in several population based studies, the analysis of MEFV, mutations of which underlie FMF1,2, has provided the first objective test of diagnostic value. However, although more than 40 MEFV mutations have been identified,3 no unambiguous mutations, such as gross gene rearrangements, nonsense, frameshift, or splice mutations, have been reported, except a single report of one MEFV allele carrying a nonsense mutation in the last coding exon.4 The most frequent mutations are conservative missense variations located in the 3′ end of the gene, a sequence that encodes a so-called B30.2/SPRY domain of unknown function. As no assay has emerged to evaluate the functional consequences of the missense mutations identified in patients with FMF, these sequence variations are considered as disease causing mutations only on the basis of their high frequency in patients.
Although the first MEFV mutations were identified 6 years ago, the pathophysiology of FMF remains unclear; and the physiological role of the marenostrin/pyrin (M/P) protein encoded by MEFV is still to be elucidated, even though several lines of indirect evidence strongly suggest the involvement of M/P in both inflammatory and apoptotic pathways.5–8 M/P has been shown to belong to an expanding family of molecules containing a protein–protein interaction domain, called a PYD domain.5,7,9,10 In M/P, this domain, which is encoded …
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