• Cécile Cazeneuve, Zaruhi Hovannesyan, David Geneviève, Hasmik Hayrapetyan, Stéphanie Papin, Emmanuelle Girodon-Boulandet, Brigitte Boissier, Josué Feingold, Karine Atayan, Tamara Sarkisian, and Serge Amselem.
• 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.
• Arthritis Rheum. 2003 Aug 1; 48 (8): 2324-31.

ObjectiveFamilial 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.MethodsThe 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.ResultsThe 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.ConclusionThese 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.

27 keywords...

hide…