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

Clin Rheumatol. 2012 Mar;31(3):493-501. doi: 10.1007/s10067-011-1876-1. Epub 2011 Nov 5.


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.

MeSH terms

  • Abdominal Pain / diagnosis
  • Abdominal Pain / genetics*
  • Adolescent
  • Adult
  • Alleles
  • Child
  • Child, Preschool
  • Cytoskeletal Proteins / genetics*
  • DNA Mutational Analysis
  • Familial Mediterranean Fever / diagnosis
  • Familial Mediterranean Fever / genetics*
  • Female
  • Fever / diagnosis
  • Fever / genetics*
  • Gene Frequency
  • Genetic Association Studies
  • Genotype
  • Humans
  • Male
  • Muscle Weakness / diagnosis
  • Muscle Weakness / genetics*
  • Mutation
  • Predictive Value of Tests
  • Pyrin
  • Retrospective Studies
  • Sensitivity and Specificity
  • Severity of Illness Index
  • Turkey


  • Cytoskeletal Proteins
  • MEFV protein, human
  • Pyrin