The clinical effect of gene mutations in familial Mediterranean fever disease

Pediatr Int. 2022 Jan;64(1):e15052. doi: 10.1111/ped.15052.


Background: Familial Mediterranean fever (FMF) is a self-limiting, autoinflammatory disease characterized by inflammation of the serosal surfaces and recurrent episodes of fever. The aim of this study is to determine the effect of genetic mutations on clinical features in children with FMF.

Methods: A total of 303 patients aged 0-18 years, who were diagnosed with FMF, according to Yalcinkaya-Özen diagnostic criteria and whose Mediterranean fever gene (MEFV) analysis was studied, were evaluated retrospectively. The clinical and demographic characteristics of the patients and the relationship between common alleles and genotypes were investigated.

Results: The most common mutation in patients was M694V heterozygous. When the patients were divided into four groups, M694V homozygous, M694V heterozygous, M694V/other allele combined heterozygous, and other mutations, Arthritis was statistically significantly higher in the group that was M694V homozygous compared to the other groups. It was observed that the presence of the M694V allele significantly increased the frequency of periodic fever, aphthous stomatitis, pharyngitis, adenitis syndrome. The frequency of arthritis was significantly higher in patients who were E148Q homozygous than in patients who were heterozygous. Appendectomy history was significantly higher in the group carrying the V726A allele.

Conclusions: FMF disease and the effect of genetics on the disease can be better understood, thanks to studies evaluating the genotype-phenotype relationship. In this regard, we believe that studies evaluating the clinical and genotype relationship with a large series are needed.

Keywords: Alleles; familial Mediterranean fever; genotype; inflammation; treatment.

MeSH terms

  • Adolescent
  • Amyloidosis* / genetics
  • Arthritis*
  • Child
  • Child, Preschool
  • Familial Mediterranean Fever* / diagnosis
  • Familial Mediterranean Fever* / genetics
  • Fever
  • Gene Frequency
  • Genotype
  • Humans
  • Infant
  • Infant, Newborn
  • Mutation
  • Pyrin / genetics
  • Retrospective Studies


  • MEFV protein, human
  • Pyrin