FMF is a recessive hereditary disorder caused by mutations in MEFV, the gene for the protein pyrin. Pyrin, produced in white blood cells, inhibits inflammation, and the FMF mutations unleash inflammation to varying degrees.
The disease manifests in painful inflammatory attacks in various parts of they body, usually accompanied by fever. Most patients have abdominal attacks and joint attacks, and chest attacks are also common.
Amyloidosis leading to kidney failure used to be common, before colchicine treatment was introduced.
It’s found in populations that originated in the eastern Mediterranean: Armenians, Sephardic Jews, North African Jews, Arabs, and Turks. Carrier frequencies can be as high as as 1 in 5 in Turks, Arabs and Armenians. Ashkenazi Jews have a fairly high carrier frequency as well, but they seem to have milder mutations that are less likely to cause serious disease.
Obviously mutations that inactivated pyrin to some degree had a significant selective advantage in these populations. There’s no other way for MEFV mutations to have become regionally common, way above mutation-selection equilibrium – particularly when they’re bad for homozygotes.
The question is, what was the advantage? Sure looks as if MEFV mutations gave protection against some infectious disease – one that significantly dinged fitness in the Middle East. The usual suspect is malaria, which has generated most of the common expensive genetic defenses 0 but it can’t be malaria. If it were, we’d see some version of FMF in Southeast Asia, or Sub-Saharan Africa, or New Guinea, and we don’t.
I’m just spitballing , running it up the flagpole to see who salutes, but I wonder if it wasn’t leishmaniasis getting out of control among early agriculturalists.