Association of clinical and genetical features in FMF with focus on MEFV strip assay sensitivity in 452 children from western Anatolia, Turkey

Abstract

The aim of this study was to determine the relationship between clinical findings and the most common mutated alleles of MEFV gene in a childhood population and to determine the sensitivity of the 12-mutation-strip assay test in familial Mediterranean fever (FMF). Records of 452 FMF children living in western Anatolia, Turkey, (12.3 ± 4.7 years mean) were retrospectively reviewed. Of the 408 patients who met the Tel-Hashomer criteria, 364 were classified into two main groups (two-mutant/one-mutant allele) either of which had three subgroups. The two-mutant allele frequency was 51% and one-mutant allele 38%; 1% had complex-mutant alleles and 10% no mutant-alleles. The mean severity score was 8.3 ± 2.5. Most common clinical features were fever (81.9%), abdominal pain (86.3%) and myalgia (58.8%), and the least common ones: diarrhea (1.7%), protracted febrile myalgia (1.2%) and acute orchitis (1.5%). We detected 33 different genotypes of the MEFV gene: the most common mutant allele was M694V followed by symptomatic allele mutation of E148Q. Although not significantly associated with clinical findings, P369S mutation was not rare (7.5%). Phenotype-genotype correlation revealed that patients with two-allele mutations had more severe clinical presentation and high constipation rate (22.5%); 32.6% of patients with M694V/M694V had splenomegaly. Acute orchitis and protracted febrile myalgia as rare clinical findings were more common in M694V homozygotes. Comparisons of clinical findings among patients with one-mutation allele were made for the first time, but no significant association was found. Positive predictive value of strip assay screening for 12 mutations was recorded as 89%. We suggest that whole sequence analysis for supportive diagnosis of FMF should be performed for selected patients only.

Mediterranean Fever Gene Mutations and Messenger Ribonucleic Acid Expressions in Pediatric Patients With Familial Mediterranean Fever in the Trakya Region of Turkey

“…[11][12][13][14][15][16] In our study group, the most frequent MEFV mutation was also M694V, and based on this result, we suggested that the distribution of MEFV gene mutations does not differ greatly between the different geographic areas of Turkey.…”

“…Öztürk et al 16 analyzed 452 pediatric FMF patients with a mean age of 12.4±4.7 (range, 2-30 years) and indicated that the common clinical findings were abdominal pain (86.3%), fever (81.9%), myalgia (58.8%) and arthritis/ arthralgia (49%). Six (2.9%) and nine (4.3%) of 207 patients carrying two mutant alleles had amyloidosis and proteinuria respectively.…”

Role of genetics in pediatric rheumatology

“…Moreover, genetic testing in the diagnosis of FMF is important in terms of preventing injury caused by amiloid-A (AA) amyloidosis, which is the most severe complication of the disease. Previous studies have shown that the risk of developing severe disease phenotype is higher in patients who are homozygous for M694V (10). It was observed that the homozygous state for M694V was a high risk factor for amiloidosis in Armenians, Israelis, and Arabs (11).…”

High frequency of E148Q sequence variation in children with familial Mediterranean fever in southeast Turkey

“…3,5,[9][10][11][12][13][14][15][16]20,21 The most common mutation characterized in Turks is the M694V mutation with the frequency of 30-50%. The E148Q mutation occurs at a frequency ranging from 1.4-11.4% according to some previous studies.…”

“…The E148Q mutation occurs at a frequency ranging from 1.4-11.4% according to some previous studies. 7,15,16,[19][20][21] Although, there were disagreement regarding whether the E148Q mutation even exhibit disease, it has been reported as disease causing mutation in FMF. 20 Two recent studies from eastern and southeast Turkey reported that the E148Q mutation occurs at frequencies of 34.1% and 30.7% in these populations, respectively, which is approximate to the frequency that we identified at 40.1%.…”