The Frequency of MEFV Gene Mutations and Genotypes in Sanliurfa Province, South-Eastern Region of Turkey, after the Syrian Civil War by Using Next Generation Sequencing and Report of a Novel Exon 4 Mutation (I423T).

Evren Gumus

doi:10.3390/jcm7050105

Abstract

Background: Familial Mediterranean Fever (FMF) is a genetic disorder characterized by recurrent episodes of fever and abdominal pain. Mutations in the Mediterranean fever (MEFV) gene are localized on the p arm of chromosome 16. Over 333 MEFV sequence variants have been identified so far in FMF patients, which occur mostly in the 2nd and 10th exons of the gene. Methods: In this study, 296 unrelated patients with clinical suspicion of FMF, which were admitted during January–December 2017, were retrospectively reviewed to identify the frequency of MEFV gene mutations by using next generation sequencing. Results: Eighteen different mutations, 45 different genotypes and a novel exon 4 (I423T) mutation were identified in this study. This mutation is the fourth mutation identified in exon 4.The most frequent mutation was R202Q, followed by M694V, E148Q, M680I, R761H, V726A and R354W. Conclusions: One of the most important aims of this study is to investigate the MEFV mutation type and genotype of migrants coming to Sanliurfa after the civil war of Syria. This study also examines the effect of the condition on the region’s gene pool and the distribution of different types of mutations. Our results indicated that MEFV mutations are highly heterogeneous in our patient population, which is consistent with the findings of other studies in our region. Previously used methods, such as Restriction Fragment Length Polymorphism (RFLP), do not define uncommon or especially novel mutations. Therefore, Next Generation Sequencing (NGS) analysis of the MEFV gene could be useful for finding novel mutations, except for those located on exon 2 and 10.

Highlights

Familial Mediterranean fever (FMF, #MIM 249100) is an autosomal recessive inherited auto-inflammatory disease characterized by fever, arthritis, peritonitis, pleuritis, myalgia, splenomegaly, erysipelas-like skin lesions and renal amyloidosis [1]
This panel contains a total of 24 primer pairs in two pools, which allows for the amplification and sequencing of all coding exons of the Mediterranean fever (MEFV) gene
There were no significant differences in the prevalence of MEFV mutation between males and females (p = 0.3)

Summary

Introduction

Familial Mediterranean fever (FMF, #MIM 249100) is an autosomal recessive inherited auto-inflammatory disease characterized by fever, arthritis, peritonitis, pleuritis, myalgia, splenomegaly, erysipelas-like skin lesions and renal amyloidosis [1]. The most frequent symptoms of this disease are abdominal pain and fever This is an autosomal recessive disease, heterozygous individuals have been shown to exhibit classical disease-related symptoms [2]. More than 100 disease-causing mutations and more than 330 sequence variants (mutations and polymorphisms) have been determined in the MEFV gene. Our results indicated that MEFV mutations are highly heterogeneous in our patient population, which is consistent with the findings of other studies in our region. Used methods, such as Restriction Fragment Length Polymorphism (RFLP), do not define uncommon or especially novel mutations. Generation Sequencing (NGS) analysis of the MEFV gene could be useful for finding novel mutations, except for those located on exon 2 and 10

Methods

Results

Conclusion