Screening of the most common MEFV variants in 416 patients of familial mediterranean fever living in Northwest of Iran.

Familial Mediterranean Fever (FMF) is an inherited disorder with an autosomal recessive pattern of inheritance. FMF is the most prevalent among ethnic populations originating from the Mediterranean region and results from pathogenic mutations in the Mediterranean fever (MEFV) gene. For the materials and methods employed in this study, a total of 416 patients from the northwestern region of Iran were screened for the presence of 18 commonly occurring variants in the MEFV gene. The screening process involved the use of multiplex amplification-ligation polymerase chain reaction coupled with fluorescently labeled DNA probes. This technique enabled the detection of single nucleotide polymorphisms, which are variations in a single nucleotide base within the MEFV gene sequence. The initial manifestation of symptoms occurred between the ages of 1 and 20 years in 63.46% of the cases studied. The four most commonly observed clinical manifestations among the patients were abdominal pain, fever, joint pain, and vomiting. Molecular analysis of 18 prevalent MEFV variants in 416 FMF patients revealed the underlying genetic causes in 242 individuals. Out of these 242 cases, 129 patients (53.3%) were heterozygous carriers of a single pathogenic variant, 19 patients (7.8%) were homozygous for a single variant, 48 patients (19.83%) were compound heterozygotes harboring two different pathogenic variants, and 46 patients (19%) exhibited multiple variants, which were classified as complex cases. The R202Q variation emerged as the most prevalent among the four genotypic groups and exhibited the highest allele frequency (39.94%), followed by E148Q (20.62%), M694V (15.14%), and V726A (15.14%). Genetic profiling of MEFV variations revealed a predominance of R202Q, with E148Q, M694V, and V726A occurring in descending order of frequency. The allele frequency of the R202Q variant exhibited a statistically significant difference when compared to other ethnic groups, with the exception of the Turkish population. Interestingly, while the M694V variant is reported as the most prevalent in several other populations and ethnic groups, in our study cohort, it emerged as the third most common variant. This finding suggests that the frequencies of specific alleles can vary substantially across different countries, populations, and ethnic groups.