title: Familial Mediterranean fever among patients from Karabakh and the diagnostic value of MEFV gene analysis in all classically affected populations.
abstract: OBJECTIVE
  Familial Mediterranean fever (FMF) is an autosomal-recessive disorder that is common in Armenian, Turkish, Arab, and Sephardic Jewish populations. Its clinical diagnosis is one of exclusion, with the patients displaying nonspecific symptoms related to serosal inflammation. MEFV gene analysis has provided the first objective diagnostic criterion for FMF. However, in the absence of an identified mutation (NI/NI genotype), both the sensitivity of the molecular analyses and the involvement of the MEFV gene in FMF are called into question. The present study was designed to further evaluate the diagnostic value of MEFV analysis in another population of Mediterranean extraction.
  
  
  METHODS
  The MEFV gene was screened for mutations in 50 patients living in Karabakh (near Armenia) who fulfilled the established criteria for FMF. In addition, we analyzed published series of patients from the above-mentioned at-risk populations.
  
  
  RESULTS
  The mutation spectrum in Karabakhian patients, which consisted of only 6 mutations (with 26% of NI alleles), differed from that reported in Armenian patients. Strikingly, among patients from Karabakh and among all classically affected populations, the distribution of genotypes differed dramatically from Hardy-Weinberg equilibrium (P = 0.0016 and P < 0.00001, respectively). These results, combined with other population genetics-based data, revealed the existence of an FMF-like condition that, depending on the patients' ancestry, was shown to affect 85-99% of those with the NI/NI genotype.
  
  
  CONCLUSIONS
  These data illuminate the meaning of negative results of MEFV analyses and show that in all populations evaluated, most patients with the NI/NI genotype had disease that mimicked FMF and was unrelated to the MEFV gene. Our findings also demonstrate the high sensitivity of a search for very few mutations in order to perform a molecular diagnosis of MEFV-related FMF.
authors.affiliation: Service de Biochimie et de Génétique Moléculaire, INSERM (Unité 468), Hôpital Henri-Mondor, 51 Avenue du Maréchal de-Lattre-de-Tassigny, Créteil F-94010, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Cazeneuve
authors.forename: Zaruhi
authors.initials: Z
authors.lastname: Hovannesyan
authors.forename: David
authors.initials: D
authors.lastname: Geneviève
authors.forename: Hasmik
authors.initials: H
authors.lastname: Hayrapetyan
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Papin
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Girodon-Boulandet
authors.forename: Brigitte
authors.initials: B
authors.lastname: Boissier
authors.forename: Josué
authors.initials: J
authors.lastname: Feingold
authors.forename: Karine
authors.initials: K
authors.lastname: Atayan
authors.forename: Tamara
authors.initials: T
authors.lastname: Sarkisian
authors.forename: Serge
authors.initials: S
authors.lastname: Amselem
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018912:Arabs / Q000235:genetics; D001136:Armenia / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D003598:Cytoskeletal Proteins; D010505:Familial Mediterranean Fever / Q000175:diagnosis* / Q000208:ethnology / Q000235:genetics*; D005260:Female; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D007585:Jews / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D011506:Proteins / Q000235:genetics*; D000071198:Pyrin
chemical_list: D003598:Cytoskeletal Proteins; C000604192:MEFV protein, human; D011506:Proteins; D000071198:Pyrin