Spectrum of MEFV gene mutations in 4,256 familial Mediterranean fever patients from Iran: a comprehensive systematic review

Abstract

Background Familial Mediterranean fever (FMF), known as a disease with a high prevalence rate among Armenian, Turkish, Jewish, and Arab descent populations, occurs as a result of pathogenic variants in mediterranean fever (MEFV) gene. The aim of this study was to review the spectrum and frequency of MEFV gene mutations reported among Iranian FMF patients. Methods After performing a systematic review of the literature and implementation of inclusion and exclusion criteria, 16 articles published between 2004 and 2020, involving 4,256 Iranian FMF patients, were included. Results A total of 38 different MEFV gene mutations were identified. The most common mutations among Iranian FMF patients were: p.M694V (c.2080A > G) (20.27%), p.E148Q (c.442G > C) (10.27%), p.V726A (c.2177T > C) (8.24%), p.M680I (both c.2040G > C and c.2040G > A) (7.20%), p.R761H (c.2282G > A) (2.1%), and p.M694I (c.2082G > A) (2. 1%). The frequencies of these mutations were significantly different in different parts of the country. Conclusions The ranks and frequencies of p.M694V, p.E148Q, p.V726A, p.M680I, and p.M694I in our population were closer to those observed in the Mediterranean countries, especially in the Middle Eastern Arab populations. Although some comprehensive studies have been performed on Azeri Turkish patients living in northwestern Iran, studies in other areas, especially in eastern Iran, have been very limited. One reason for this observation could be due to the low frequency of FMF patients in those areas. Regardless of the reason for this, the exact spectrum and frequency of MEFV gene mutations in Iranian FMF patients remain unclear. Therefore, comprehensive future studies in different parts of the country are recommended.