MEFV mutations and their relation to major clinical symptoms of Familial Mediterranean Fever.

Familial Mediterranean fever is a common hereditary disease in Turkey. To date, different mutational spectrum of MEFV gene was observed in studies carried out in different regions of Turkey but in most of these studies association of clinical symptoms of FMF to mutant genotypes have not been investigated in details. Here we report the MEFV gene variations in exons 2, 3, 5 and 10 and their relations to major clinical symptoms of FMF in 514 unrelated (245 males and 269 females) Turkish patients. MEFV mutations were found in 45% (n=230) of patients and 55% (n=284) of patients did not have any mutations. One hundred and thirty-seven (60%) patients were heterozygous, 57 (24.7%) patients were compound heterozygous, 33 (14%) patients were homozygous and 3 (1.3%) patients were having a complex genotype. Allele frequencies of MEFV mutations were M694V (48%), E148Q (18%), M680I (15%), V726A (12.5%), P369S (3.3%), R761H (0.9), K695R (0.9), E148V (0.9) and A744S (0.5%). Abdominal pain (76%) and fever (58%) were two most seen complications among patients followed by arthritis (28%) and chest pain (19%). Almost all major clinical symptoms of FMF were higher in patients with one or more M694V or M680I mutant allele. In contrast, patients having E148Q or V726A mutant allele showed fewer clinical FMF symptoms. Patients with P369S have higher abdominal pain, chest pain and fever than expected. Arthritis was high in K695R heterozygous genotype. One hundred and eighteen patients were carrying more than one polymorphic allele. The most common polymorphism was R202Q (13%). In addition, a novel heterozygous polymorphism at 564th nucleotide (C>T) of exon2 were found in 2 patients.