Relationship between clinical findings and genetic mutations in patients with familial Mediterranean fever

Abstract

BackgroundFamilial Mediterranean fever (FMF) is one of the most frequent genetic diseases encountered in the Mediterranean region. We aimed to investigate the correlation between genetic mutations and the clinical findings in 562 patients with FMF.MethodsIn this retrospective cross-sectional study conducted with patients’ files between 2006, and 2013, reverse hybridization assay for MEFV gene mutations was used and the 12 most frequent mutations were screened. Mutation types and clinical findings were compared with variance analysis.ResultsThe mean age was 6.9 ± 3.4 years (range, 1.8-11.6 years). The most common symptom was fever (97.3 %). Thirty-four of the patients (6.04 %) were admitted with periodic fever only. Of these patients, M694V was the most common mutation type (73.5 %). The percentage of the patients predominantly presenting with recurrent abdominal pain was 77.78 % and the most frequent mutations were M694V and E148Q. The rate of arthritis and arthralgia was significantly higher in patients with M694V and E148Q mutations. Chest pain was reported more often in patients homozygous for M694V (61.4 %). Pericardial effusion was documented in the echocardiography of 10.9 % of the 229 children with chest pain. Some patients had both FMF and Henoch Schönlein purpura (HSP), and were more likely to harbor either homozygote M694V or E148Q mutations. The frequency of episodes was higher in patients with homozygous M694V mutations (number of attacks = 4.4 ± 1.6/month). Proteinuria was detected in 106 patients of cases (29.2 %), at an average of 854 ± 145 mg/L. Most of the patients with proteinuria and elevated serum amyloid-A had homozygous M694V mutation.ConclusionThe most common mutation in children in Turkey with FMF is the M694V mutation. Recurrent abdominal pain, arthritis or arthralgia, chest pain, and pericarditis were commonly seen in patients with M694V and E148Q mutations.

MEFV Mutation Frequency in Pediatric Patients with Familial Mediterranean Fever and its Relationship with Clinical Phenotypes in Marmara Region of Turkey

“…The complaints that accompany R202Q, E148Q, and M694V mutations most frequently were abdominal pain, arthralgia and high fever, which is consistent with the literature (32,33).…”

Clinical features and disease severity of Turkish FMF children carrying E148Q mutation

“…Topaloglu et al from Turkey found that the severity of disease could be moderate/severe in patients with homozygous E148Q mutation in addition to high colchicine response. Another recent study revealed clinically severe disease in one fourth of heterozygous mutated Turkish patients for E148Q . All these results demonstrate that E148Q mutation usually produces a milder disease but may also have severe findings.…”

“…Despite the fact that the frequency of E148Q differs according to ethnicity, most studies from different ethnic communities and countries support the idea of having a phenotypic effect of E148Q . In recent studies, E148Q allele frequency was found 25% in Jewish, Arab, and Druze patients living in Israel and 20% in Turkish FMF patients living in Turkey . It was also reported that 34% Japanese FMF patients and 17% of Azeri Turk patients living in Iran had E148Q mutation .…”

Lack of clear and univocal genotype‐phenotype correlation in familial Mediterranean fever patients: A systematic review

“…[58][59][60][61][62] Supporting that M694V/M694V genotype might be associated with more clinically severe course of the disease, authors reported variations in acute-phase reactants during attack and attackfree periods. 63,64 However, although these findings were confirmed in further studies, [22][23][24] other authors were not in agreement with these results. 65 Particularly, unexpectedly though, despite the fact that it has been observed only in the patients with amyloidosis, studies did not link the M694V/M694V genotype to the renal complication.…”

“…16 Whether some authors looked at E148Q as a benign polymorphism, other authors considered it as a disease-causing mild mutation with less penetrance and cumulative aggravating effect. 22,25,26 Moreover, the complicated genotype-phenotype correlation is further compounded by several doubts on mode of inheritance of the disease. 27 Because of the autosomal recessive nature, subjects with clinical FMF should have 2 mutations in both alleles.…”