Three Family Members with Familial Mediterranean Fever Carrying the M694V Mutation Showed Different Clinical Presentations

Abstract

Familial Mediterranean fever (FMF) is an inherited disease characterized by recurrent episodes of fever and serositis. FMF is caused by mutations in the MEFV gene that encodes pyrin/marenostrin. The 5 most frequent mutations are M694V, M694I, V726A, M680I and E148Q. Here, we reported 3 FMF patients, a sister and two brothers, who have the same M694V mutation with different clinical presentations. While the sister presented with abdominal pain, one of the brothers presented with erysipelas-like erythema and the other brother with bilateral sacroiliitis. Here, we report the different clinical courses of FMF in a family carrying the same M694V mutation.

Genetic Profile of Patients with Familial Mediterranean Fever (FMF): Single Center Experience at King Hussein Medical Center (KHMC)

“…MFEV gene product is a 781 aa protein known as pyrin or marenostrin ( 8 ), that has a regulatory effect on inflammation, and so abnormality in its production would produce an inappropriate inflammatory reaction ( 9 ) as seen in FMF manifested as recurrent attacks of fever, arthritis, pleuritis and sterile peritonitis ( 11 ). Amyloidosis is the most sever complication of the disease ( 4 , 12 ), specially renal amyloidosis leading to an end stage renal disease ( 5 ), daily colchicines is the main treatment ( 13 ) showed to lower the severity and frequency of attacks and the chance of developing amyloidosis ( 1 ).…”

“…The most frequent mutations among Arab, Turks, Jews and Iranians are M694V, E148Q, M680I, M694V and V726A ( 3 , 10 , 12 - 15 ). The order and percentage however is different among each population from the above mentioned ones, and the mutations differ in penertrance and correlation with severity of clinical symptoms, with E148Q having the least penertrance and recognized to have a milder clinical course ( 2 , 9 ), while M694V recognized as the most severe and with increased risk of amyloidosis ( 4 , 14 , 16 ).…”

Rezidivierende Monarthritiden kleiner Gelenke: atypisches Leitsymptom eines spät erkannten familiären Mittelmeerfiebers

“…Eine Morgensteifigkeit, Wetterfühligkeit und Fieber werden verneint. (5). Auch gibt es homozygote und compound-heterozygote Mutationsträger, die keinerlei Symptome haben und andererseits klinisch eindeutige FMF-Patienten, die nur eine oder keine Mutation im MEFV-Gen aufweisen.…”

Rheumatoid Arthritis and Familial Mediterranean Fever or Sacroiliitis Accompanied by FMF

“…Mutations in the pyrin-encoding gene Mediterranean fever (MEFV) on chromosome 16p13.3 are responsible for clinical findings and different phenotypical features [2, 3]. Pyrin proteins affected by these mutations alter inflammatory processes via some cytokines, especially interleukin-1 β .…”

“…Inflammatory processes can cause arthritis (in any joints, including the sacroiliac joint), fever, serositis, and erysipelas-like skin lesions. Nevertheless, phenotypical variations may be seen among patients having the same genotypes [2, 3]. Spinal (i.e., sacroiliitis) and peripheral joint (i.e., knee arthritis) involvements of FMF can be resembling spondyloarthropathies (SpA) features [4].…”