Beheshtian Maryam, Izadi Nasim, Kriegshauser Gernot, Kahrizi Kimia, Mehr Elham Parsi, Rostami Maryam, Hosseini Masoumeh, Azad Maryam, Montajabiniat Mona, Kariminejad Ariana, Nemeth Stefan, Oberkanins Christian, Najmabadi Hossein
Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Koodakyar Alley, Daneshjoo Blvd., Evin St., 1985713834 Tehran,
J Genet. 2016 Sep;95(3):667-74. doi: 10.1007/s12041-016-0682-6.
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.
家族性地中海热（FMF）是一种由MEFV基因突变引起的遗传性自身炎症性疾病。该疾病在亚美尼亚人、土耳其人、犹太人和中东阿拉伯人群中尤为常见。为了确定不同伊朗人群中常见MEFV突变的频率和谱型，我们调查了一组208名未经选择的无症状个体和743名FMF患者。通过聚合酶链反应（PCR）和反向杂交（FMF StripAssay，ViennaLab，奥地利维也纳）对951份样本进行了12种MEFV突变检测。对39例患者的所有MEFV基因外显子进行了验证性双脱氧测序。57名（27.4%）健康个体携带MEFV突变等位基因。391名（52.6%）FMF患者被发现存在一种（172/743；23.1%）、两种或三种MEFV突变。通过双脱氧测序，可鉴定出三种新的变异体A66P、R202W和H300Q。我们的分析显示，健康伊朗人的等位基因频率和携带率分别为15.6%和27.4%。与邻国亚美尼亚相比仍处于中等水平，但高于土耳其或伊拉克，这些数据表明FMF在伊朗人群中非常普遍。E148Q在健康个体组中最常见，而M694V是FMF患者中最常见的突变，从而证实了先前关于中东地区MEFV突变谱的研究。因此，MEFV突变在不同种族的健康伊朗个体中很常见。基于这一发现，应提高对FMF的认识，并考虑到伊朗人口的多民族性质，实施强化的携带者筛查计划。
