Familial Mediterranean fever: High gene frequency and heterogeneous disease among an Israeli-Arab population

Objective. Familial Mediterranean fever (FMF) is an autosomal recessive dis ease that primarily affects non-Ashkenazi Jews, Armenians, Arabs, and Turks . The FMF (MEFV) gene responsible for the disease has been recently identif ied. Four missense mutations in exon 10 of the FMF gene seem to account for 86% of the DNA variations identified in patients with FMF. We conducted a phenotype/genotype correlation study in a homogenous population of Israeli- Moslem Arab patients with FMF and performed a mutational screening analysis on DNA samples from healthy individuals of this ethnic group. Methods. Sixty-five patients clinically diagnosed as having FMF underwent m olecular genetic studies using polymerase chain reaction and restriction en donuclease digestion methods to detect the presence of the 4 mutations (M69 4V, V726A, M680I, M694I). We then correlated the presence of each mutation with age of onset, clinical manifestations, and disease severity; patients whose allelic combination included M694V were then excluded from further st atistical analysis, since the association of severe disease with the M694V allele has already been shown. In addition, we screened fur FMF mutations t he DNA samples from 318 healthy Moslem Arab individuals fur the presence of these mutations. Results. Among the 65 patients who were clinically diagnosed as having FMF, 78.5% had one or 2 mutation-bearing chromosomes. The most prevalent mutati on was V736A, followed by M680I, M694V, and M694I. No significant differenc e in phenotypic characteristics was found between the patients with the div erse mutations. The total carrier frequency for the 4 mutations was 10.4% ( 95% confidence interval 0.07 to 0.137). Conclusion. A high FMF gene frequency was found among an Israeli-Moslem Ara b population. Among the FMF patients from this ethnic group, several mutati ons were detected, none of which was found to correlate with a severe cours e of the disease.