MEFV

Familial Mediterranean fever

More than 80 MEFV gene variants (also known as mutations) have been found to cause familial Mediterranean fever. A few variants delete small amounts of DNA from the MEFV gene, which can lead to an abnormally small, nonfunctional protein. Most MEFV gene variants, however, change one of the protein building blocks (amino acids) used to make pyrin. The most common variant replaces the amino acid methionine with the amino acid valine at protein position 694 (written as Met694Val or M694V). Among people with familial Mediterranean fever, this particular variant is also associated with an increased risk of developing amyloidosis, a complication in which abnormal protein deposits can lead to kidney failure. Some evidence suggests that normal variations in another gene, called SAA1, can further modify the risk of developing amyloidosis among people with the M694V change.

MEFV gene variants lead to reduced amounts of pyrin or a malformed pyrin protein that cannot function properly.  As a result, pyrin cannot perform its presumed role in controlling inflammation, leading to an inappropriate or prolonged inflammatory response. Fever and inflammation in the abdomen, chest, joints, or skin are signs of familial Mediterranean fever.