Molecular and in Silico Analysis of <i>MEFV</i> Variants in Familial Mediterranean Fever Patients in Southwest Iran

Abstract

Familial Mediterranean Fever (FMF) is classified as an autoinflammatory genetic disease inherited by mutations in <em>MEFV</em>. These mutations can affect the dysregulation of inflammatory processes in the human body and lead to fever and pain in the chest and abdomen. Many known missense mutations in <em>MEFV</em> are linked to FMF disease. Mutations in <em>MEFV</em> in most cases are located on the short arm of chromosome 16 and can impair the function of the pyrin protein. In this research, we aimed to examine the entire exons of <em>MEFV</em> for 13 cases (8 females and 5 males) with FMF diagnosis from Southwest Iran. Hence, we amplified and sequenced the exons of <em>MEFV</em> and then, in-silico analysis of detected changes was applied to estimate the probability of pathogenicity for the identified variants. Finally, we found five single nucleotide substitutions, including M694V (c.2080A>G), R202Q (c.605G>A), E447G (c.1430A>G), E148Q (c.442G>C), and V726A (c.2177T>C), in the under-represented patients. The most frequent mutations in our study were R202Q (38.46%) within exon 2 and M694V (30.7%) within exon 10. Other mutations accounted for a further 23% of the alleles, including E477G (7.6%), E148Q (7.6%), and V726A (7.6%). According to the <em>in-silico</em> analyses, including variation pathogenicity, protein structure, and allele frequency assessments, we concluded that all these variants could be considered in FMF molecular profiling in southwest Iran.