MEFV gene compound heterozygous mutations in familial Mediterranean fever phenotype: a retrospective clinical and molecular study.

Background: Familial Mediterranean fever (FMF) is an autosomal-recessive inherited inflammatory disease caused by mutations in the MEFV gene that encodes pyrin/marenostrin. It is characterized by recurrent short episodes of fever, abdominal pain and serositis affecting mainly Mediterranean and Middle Eastern populations. We determined the frequency of the compound heterozygous mutations which has been rarely reported. The present study not only investigated clinical features of child-onset FMF patients with compound heterozygous mutations but also determined whether there is a phenotype-genotype correlation in the same patient population.

Methods: The medical records of 66 heterozygous patients with FMF were retrospectively reviewed and assessed. Patients were investigated regarding the mutation type, clinical characteristics at the time of inflammatory attacks such as fever, abdominal pain, arthritis, chest pain, erysipelas-like erythema and oedema, epidemiological data, consanguinity, severity score and family history of FMF and amyloidosis.

Results: The most frequent mutation was M694V, identified in 32% of the alleles examined, followed by E148Q in 20.6%, V726A in 17% and M680I in 14.5%, respectively. Consequently, we determined that P369S (n = 10; 8%) was the most frequent rare mutation in Turkish FMF patients. Frequency of the other rare mutations were R761H (3%), F479L (3%), A744S (1.5%) and K695R (0.7%). Fever was seen in 96.5%, abdominal pain in 98.5%, arthralgia in 85%, chest pain in 45.5% and erysipelas-like lesions in 23%. None of these patients had amyloidosis, but 16 had a family history of chronic renal failure, 44% had vomiting and 35% had diarrhoea during the attack. Although regular colchicine treatment was effective in 83% of the patients, the percentage of patients that did not start colchicine therapy was 18%. In addition, the patients were divided into four groups according to the presence of the mutation types and we compared genotype-phenotype correlations.

Conclusions: We suggest that regular colchicine therapy may be administered to symptomatic patients with MEVF gene compound heterozygous mutations, regardless of the mutation type.