title: 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.
authors.affiliation: Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Koodakyar Alley, Daneshjoo Blvd., Evin St., 1985713834 Tehran, Iran.hnajm12@yahoo.com.
authors.forename: Maryam
authors.initials: M
authors.lastname: Beheshtian
authors.forename: Nasim
authors.initials: N
authors.lastname: Izadi
authors.forename: Gernot
authors.initials: G
authors.lastname: Kriegshauser
authors.forename: Kimia
authors.initials: K
authors.lastname: Kahrizi
authors.forename: Elham Parsi
authors.initials: EP
authors.lastname: Mehr
authors.forename: Maryam
authors.initials: M
authors.lastname: Rostami
authors.forename: Masoumeh
authors.initials: M
authors.lastname: Hosseini
authors.forename: Maryam
authors.initials: M
authors.lastname: Azad
authors.forename: Mona
authors.initials: M
authors.lastname: Montajabiniat
authors.forename: Ariana
authors.initials: A
authors.lastname: Kariminejad
authors.forename: Stefan
authors.initials: S
authors.lastname: Nemeth
authors.forename: Christian
authors.initials: C
authors.lastname: Oberkanins
authors.forename: Hossein
authors.initials: H
authors.lastname: Najmabadi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005006:Ethnicity; D005091:Exons; D010505:Familial Mediterranean Fever / Q000453:epidemiology* / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D007223:Infant; D007492:Iran / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D015995:Prevalence; D000071198:Pyrin / Q000235:genetics*
chemical_list: C000604192:MEFV protein, human; D000071198:Pyrin