Genetically determined recurrent fevers

The usefulness of molecular diagnosis is now well established for genetical ly determined recurrent fevers. In familial Mediterranean fever, the severi ty of the disease and the risk of renal amyloidosis are correlated with mut ations in MEFV, and the serum amyloid-associated protein (SAA)1 alpha/alpha allele is a modifying factor for amyloidosis. Study of the genes in variou s species shows that the human mutations represent a reappearance of the an cestral amino acid state and the B30-2 domain, where most human mutations a re 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 descr ibed, some are associated with an incomplete penetrance.