Clinical disease among patients heterozygous for familial Mediterranean fever

Arthritis Rheum. 2009 Jun;60(6):1862-6. doi: 10.1002/art.24570.


Objective: To define the molecular basis of familial Mediterranean fever (FMF) in patients with only 1 mutation in the MEFV gene.

Methods: Genetic analysis was performed in 20 FMF patients, including full sequencing of complementary DNA (cDNA) samples and multiplex ligation-dependent probe amplification analysis. In patients with first-degree relatives with FMF, haplotype analysis was also performed.

Results: A second mutation was found in 2 patients. In the other 18 patients, we could not identify additional mutations, large genomic deletions, or duplications. Analysis of single-nucleotide polymorphisms along the cDNA ruled out a lack of expression of 1 of the alleles. In 2 of the 3 families in which more than 1 sibling had FMF, we showed that the affected siblings inherited a different MEFV allele from the parent who did not have the MEFV mutation.

Conclusion: These findings are highly consistent with the existence of a clinical phenotype among some patients who are heterozygous for FMF and could explain the vertical transmission in some families. A single mutation in the MEFV gene may be much more common than was previously thought and may include up to 25% of patients who are diagnosed as having FMF.

MeSH terms

  • Adolescent
  • Adult
  • Alleles
  • Child
  • Child, Preschool
  • Cytoskeletal Proteins / genetics*
  • DNA / genetics
  • Familial Mediterranean Fever / diagnosis*
  • Familial Mediterranean Fever / genetics*
  • Female
  • Genetic Testing
  • Haplotypes / genetics
  • Heterozygote*
  • Humans
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Pedigree
  • Phenotype
  • Polymorphism, Single Nucleotide / genetics
  • Pyrin
  • Young Adult


  • Cytoskeletal Proteins
  • MEFV protein, human
  • Pyrin
  • DNA