Genotype Mutations in Egyptian Children with Familial Mediterranean Fever: Clinical Profile, and Response to Colchicine

Abstract

Background: Familial Mediterranean fever (FMF) is an autosomal recessive autoinflammatory disorder that is characterized by recurrent episodes of fever, peritonitis, pleuritis, pericarditis, and/or arthritis. MEFV is the responsible gene for FMF, of which more than 310 mutations have been reported; M694V, M694I, V726A, E148Q, and M680I mutations are the five most frequent mutations responsible for the majority of FMF patients in the Middle East. Aim: To study the genetic background of FMF among Egyptian children to detect the most frequent MEFV mutations and to study the response of colchicine therapy with different gene mutations. Methods: This cross-sectional study included 109 pediatric patients already diagnosed clinically with FMF, and were following-up at the Rheumatology Outpatient Clinic, Children’s Hospital, Cairo University. Results: Out of 109 patients, 95 had positive-MEFV mutation (87.16%), of which the most frequent mutations were E148Q (24/95 patients, 25.26%), V726A (19/95 patients, 20%), M680I (19/95 patients, 20%), M694V (17/95 patients, 17.89%), and M694I (7 patients, 7.37%). A better response to colchicine therapy was noted in E148Q mutation; on the other hand, more severe cases were reported with M694V mutations. Conclusion: E148Q, V726A, M680I, M694V and M694I mutations are the most frequent mutations denoting the heterogeneous mutation pattern and the milder form of the disease among Egyptian patients. M694V mutations may indicate a more severe disease score.

Genetic and Epigenetic Regulation of MEFV Gene and Their Impact on Clinical Outcome in Auto-Inflammatory Familial Mediterranean Fever Patients

“…In agreement with previous studies in the Egyptian population [38,40], the heterozygous genotype was more predominant in our study, followed by homozygous and compound heterozygous. Additionally, no significant difference was shown concerning the association of the MEFV exon 2 methylation% and the pyrin level with genotyping status among FMF patients, which agrees with previous studies [10,26] and may be due to the MEFV exon 2 splicing [15,16].…”

“…The association of epigenetic modifications and autoimmune disorders has been an area of active research over the last decade [10]. Several studies have addressed FMF disease in the Egyptian population [20,[37][38][39][40][41][42][43], but the novel portrayals in our study are detecting the methylation% of the MEFV exon 2 and the pyrin concentration in FMF Egyp-…”

“…The association of epigenetic modifications and autoimmune disorders has been an area of active research over the last decade [10]. Several studies have addressed FMF disease in the Egyptian population [20,[37][38][39][40][41][42][43], but the novel portrayals in our study are detecting the methylation% of the MEFV exon 2 and the pyrin concentration in FMF Egyptian patients, and whether we could target DNA methylation and pyrin level as future diagnostic and prognostic biomarkers by studying their relations with gender, consanguineous marriage, similarly affected family members, phenotype, disease severity, genotype, biomarkers, and drug response.…”

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

“…In addition, while p.M694I and p.V726A are known to be common among Arab populations in the Middle East [44], p.M680I is common in Turkish FMF patients [29,30]. The frequency of these mutations is not the same among North African countries [44][45][46][47][48][49]. In total, it seems that the order of five most common MEFV gene mutations among Iranian FMF patients is most similar to that observed in Middle Eastern Arab populations [44].…”

Recurrent Fever with Oral Lesions in Egyptian Children: A Familial Mediterranean Fever Diagnosis Not to Be Missed

“…In an Egyptian study, Talaat et al evaluated 70 patients with FMF; they demonstrated that E148Q, V726A, and M680I were the most common mutations and were detected in 20%, 15.7%, and 14.3% of patients, respectively [ 24 ]. Another Egyptian study reported that E148Q is the most frequent mutation [ 29 ]. In the Mediterranean region, FMF is very common, and the mutation frequency shows marked variability.…”