Non-founder mutations in the MEFV gene establish this gene as the cause of familial Mediterranean fever (FMF)

Hum Mol Genet. 1998 Aug;7(8):1317-25. doi: 10.1093/hmg/7.8.1317.


Familial Mediterranean fever (FMF) is an autosomal recessive disorder characterized by recurring attacks of fever and serositis. It affects primarily North African Jews, Armenians, Turks and Arabs, in which a founder effect has been demonstrated. The marenostrin-pyrin-encoding gene has been proposed as a candidate gene for the disease ( MEFV ), on the basis of the identification of putative mutations clustered in exon 10 (M680V, M694I, M694V and V726A), each segregating with one ancestral haplotype. In a search for additional MEFV mutations in 120 apparently non-founder FMF chromosomes, we observed eight novel mutations in exon 2 (E148Q, E167D and T267I), exon 5 (F479L) and exon 10 (I692del K695R, A744S and R761H). Except for E148Q and K695R, all mutations were found in a single chromosome. Mutation E148Q was found in all ethnic groups studied and in association with a novel ancestral haplotype in non-Ashkenazi Jews (S2). Altogether, these new findings definitively establish the marenostrin/pyrin-encoding gene as the MEFV locus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Africa, Northern / ethnology
  • Amino Acid Sequence
  • Cytoskeletal Proteins
  • Exons / genetics
  • Familial Mediterranean Fever / genetics*
  • Haplotypes
  • Humans
  • Molecular Sequence Data
  • Mutation*
  • Proteins / genetics*
  • Pyrin
  • Sequence Analysis


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