Prevalence of common MEFV mutations and carrier frequencies in a large cohort of Iranian populations

Abstract

Familial Mediterranean fever (FMF) is a hereditary autoinflammatory disorder caused by mutations in the MEFV gene. The disease is especially common among Armenian, Turkish, Jewish and Middle East Arab populations. To identify the frequency and the spectrum of common MEFV mutations in different Iranian populations, we investigated a cohort of 208 unselected asymptomatic individuals and 743 FMF patients. Nine hundred and fifty-one samples were analysed for the presence of 12 MEFV mutations by PCR and reverse-hybridization (FMF StripAssay, ViennaLab, Vienna, Austria). Confirmatory dideoxy sequencing of all MEFV gene exons was performed for 39 patients. Fifty-seven (27.4%) healthy individual carried mutant MEFV alleles. Three hundred and ninety-one (52.6%) FMF patients were found positive for either one (172/743; 23.1%), two or three MEFV mutations. Using dideoxy sequencing, three novel variants, A66P, R202W and H300Q, could be identified. Our analysis revealed an allele frequency and carrier rate of 15.6 and 27.4%, respectively, among healthy Iranians. Still moderate compared to neighbouring Armenia, but higher than in Turkey or Iraq, these data suggest that FMF is remarkably common among Iranian populations. E148Q was most frequent in the group of healthy individuals, whereas M694V was the most common mutation among FMF patients, thereby corroborating previous studies on MEFV mutational spectra in the Middle East. Accordingly, MEFV mutations are frequent in healthy Iranian individuals across different ethnic groups. Based on this finding, the awareness for FMF and the implementation of augmented carrier screening programmes considering the multiethnic nature of the Iranian population should be promoted.

Expanded carrier screening for preconception reproductive risk assessment: Prevalence of carrier status in a Mexican population

“…A 2.36% prevalence for variants in the MEFV gene was found in our population. Published data about the prevalence of these familiar Mediterranean fever causing variants in Mexican population is lacking, although our study's finding is comparable with those reported in Middle Eastern populations …”

A novel cluster of patients with Familial Mediterranean Fever (FMF) in southern Italy

“…The prevalence of M694I and of the rare form of M680I (M680I G > A) were also relatively high in Italians (10% and 8% respectively). These studies and others [16,17] show that the most prevalent mutations (R761H and K695R) in our study (in Apulia and Basilicata) are actually very rare in the neighbouring countries and islands as well as in relatively far states such as Iran. When we looked for possible sources for the R761H and the K695R mutations (found among our patients), we found that among Turkish Aegean patients with FMF allelic frequencies for the most common mutations were 47Á60% (M694V), 16Á75% (E148Q), 12Á95% (V726A) and 11Á94% (M680I G/C).…”

“…The missense mutations R761H (3Á73%) and A744S (2Á24%) were identified as the rarest [15]. These studies and others [16,17] show that the most prevalent mutations (R761H and K695R) in our study (in Apulia and Basilicata) are actually very rare in the neighbouring countries and islands as well as in relatively far states such as Iran. This observation suggests that the origin of the FMF population in Altamura and Matera is probably from small closed families who carried these rare mutations and emigrated together from neighbouring countries or islands (Turkey, Cyprus etc) and settled in these two towns.…”

Increased frequency of MEFV genes in patients with epigastric pain syndrome

“…However, V726A homozygotes and compound heterozygotes for the V726A/E148Q variants are associated with severe disease, and patients can develop renal amyloidosis. Hence, the authors proposed that patients carrying this complex allele should have been given colchicine prophylaxis [ 9 , 34 ]. In the present study, V726A is the third most common mutation with a frequency of 9.3%.…”