Phenotype-genotype correlation in familial Mediterranean fever: evidence for an association between Met694Val and amyloidosis

Eur J Hum Genet. 1999 Apr;7(3):287-92. doi: 10.1038/sj.ejhg.5200303.

Abstract

Familial Mediterranean fever (FMF) is an autosomal recessive disease characterised by recurrent attacks of inflammation of serosal membranes. Amyloidosis is the most severe complication of the disease. The aim of this study was to investigate the genotype-phenotype correlation and specifically the association between amyloidosis and the four common mutations in exon 10 of the gene causing FMF (MEFV) in a total of 83 FMF families from three ethnic groups: North African Jews, Armenians and Turks. A significant association was found between amyloidosis and the specific mutation at the MEFV gene: Met694Val (RR = 1.41, P = 0.02). Amyloidosis was present in 18 out of 87 homozygous FMF patients (20.7%) and in only two out of the 41 compound heterozygous FMF patients (4.9%). No patients carrying other mutations had amyloidosis. There was no significant association between the various mutations and the type or severity of the FMF symptoms. This finding underscores the importance of performing molecular studies on all suspect FMF patients. In addition to providing accurate diagnosis, these tests allow identification of presymptomatic genetically affected individuals, detection of carriers and assessment of the risk for amyloidosis in later life.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Amyloidosis / genetics*
  • Child
  • Child, Preschool
  • Cytoskeletal Proteins
  • Familial Mediterranean Fever / genetics*
  • Familial Mediterranean Fever / physiopathology
  • Female
  • Genotype
  • Humans
  • Male
  • Methionine / genetics*
  • Phenotype
  • Proteins / genetics*
  • Pyrin
  • Valine / genetics*

Substances

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