Genetically determined recurrent fevers

Abstract

The usefulness of molecular diagnosis is now well established for genetically determined recurrent fevers. In familial Mediterranean fever, the severity of the disease and the risk of renal amyloidosis are correlated with mutations in MEFV, and the serum amyloid-associated protein (SAA)1 alpha/alpha allele is a modifying factor for amyloidosis. Study of the genes in various species shows that the human mutations represent a reappearance of the ancestral amino acid state and the B30-2 domain, where most human mutations are localized, is absent in the rat and mouse proteins. Since the discovery of the responsible gene, TNF-receptor-associated periodic syndrome seems to be more frequent than previously considered. Among the new mutations described, some are associated with an incomplete penetrance.