title: Analysis of the three most common MEFV mutations in 412 patients with familial Mediterranean fever.
abstract: BACKGROUND
  Familial Mediterranean fever is an autosomal recessive disease characterized by recurrent attacks of fever and serositis. The disease is caused by mutations in the MEFV gene, presumed to act as a down-regulator of inflammation within the polymorphonuclear cells.
  
  
  OBJECTIVE
  To present the results of 412 FMF patients genotyped for three MEFV mutations, M694V, V726A and E148Q.
  
  
  RESULTS
  The most frequent mutation, M694V, was detected in 47% of the carrier chromosomes. This mutation, especially common among North African Jewish FMF patients, was not found in any of the Ashkenazi (East European origin) patients. Overall, one of the three mutations was detected in 70% of the carrier chromosomes. M694V/M694V was the most common genotype (27%), followed by M694V/V726A (16%). The full genotype could be assessed in 57% of the patients, and one disease-causing mutation in an additional 26%. Only one patient with the E148Q/E148Q genotype was detected despite a high carrier rate for this mutation in the Jewish population, a finding consistent with a low penetrance of this genotype. The M694V/M694V genotype was observed in 15 patients with amyloidosis compared to 4 amyloidosis patients with other genotypes (P < 0.0001).
  
  
  CONCLUSIONS
  Because of low penetrance and as yet other undetermined reasons, mutation analysis of the most common MEFV mutations supports a clinical diagnosis in only about 60% of patients with definite FMF.
authors.affiliation: Heller Institute of Medical Research, Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: Nurit
authors.initials: N
authors.lastname: Zaks
authors.forename: Yael
authors.initials: Y
authors.lastname: Shinar
authors.forename: Shai
authors.initials: S
authors.lastname: Padeh
authors.forename: Merav
authors.initials: M
authors.lastname: Lidar
authors.forename: Adam
authors.initials: A
authors.lastname: Mor
authors.forename: Irena
authors.initials: I
authors.lastname: Tokov
authors.forename: Mordechai
authors.initials: M
authors.lastname: Pras
authors.forename: Pnina
authors.initials: P
authors.lastname: Langevitz
authors.forename: Elon
authors.initials: E
authors.lastname: Pras
authors.forename: Avi
authors.initials: A
authors.lastname: Livneh
mesh_terms: D000686:Amyloidosis / Q000235:genetics; D016009:Chi-Square Distribution; D003598:Cytoskeletal Proteins; D004252:DNA Mutational Analysis; D010505:Familial Mediterranean Fever / Q000235:genetics*; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D009154:Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000235:genetics*; D000071198:Pyrin
chemical_list: D003598:Cytoskeletal Proteins; C000604192:MEFV protein, human; D011506:Proteins; D000071198:Pyrin