The Population Genetics of Familial Mediterranean Fever: A Meta‐Analysis Study

Abstract

SummaryOur aim was to construct a Familial Mediterranean Fever (FMF) cumulative database and to propose a MEFV based phylogenetic tree. Data were collected from published studies. A meta-analysis based on 16,756 chromosomes from FMF patients and normal individuals from 14 affected populations was performed. Arlequin 2.0 and Phylip 3.2 software were used for population genetics analysis and phylogenetic tree construction.We have shown that MEFV mutations are distributed non-uniformly along the Mediterranean Sea area. The most frequent mutations detected in FMF patients are M694V

Enhanced exon 2 skipping caused by c.910G>A variant and alternative splicing of MEFV genes in two independent cases of familial Mediterranean fever

“…The patients had homozygous c.910G[A variant, which results in excessive alternative splicing of exon 2 of the MEFV gene. To date, essentially all MEFV mutations of FMF patients are missense mutations [3,4,24,25]. There has been no known report of nonsense mutation or mutation with exon skipping.…”

“…Mutations of the MEFV gene are concentrated within exon 10, and the major mutations-M694V, V726A, M694I, and M680I-comprise [74% of all reported mutations [3,9,10]. Notably, all of these mutations are missense, and no case has been reported with nonsense mutation or splice variants.…”

“…Early diagnosis and appropriate therapeutic intervention is therefore mandatory to avoid these consequences. Although the vast majority of reported cases of FMF are from countries around the Mediterranean basin [3], as the name implies, patients from other part of the world are increasing in number [4,5]. To date, more than 50 mutations in the FMF-associated gene (MEFV) have been identified in Japan since 1976 [6][7][8].…”

A case of familial Mediterranean fever associated with compound heterozygosity for the pyrin variant L110P-E148Q/M680I in Japan

“…So far, 184 mutations and polymorphisms of this gene have been identified [7]. Five common mutations (M694V, M694I, M680I, V726A, and E148Q) account for the vast majority of FMF mutations [8][9][10]. The clinical symptoms of FMF vary according to the mutations of MEFV.…”

Familial Mediterranean fever in Russia: Experience of the Federal Rheumatology Center

“…Однако распро-страненность ССЛ не ограничивается только этими этноса-ми. Во многом благодаря многовековой миграции населе-ния с мутацией гена MEFV болезнь распространились по всему миру и сегодня нередко встречается в европейских странах: Греции, Италии (преимущественно Южной), Ис-пании, Франции, Германии [19,20]. Имеются сообщения о случаях ССЛ в таком удаленном от Средиземноморья реги-оне, как Дальний Восток (Япония) [21].…”