Common Mediterranean Fever Gene Mutations in the Azeri Turkish Population of Iran

Ankylosing spondylitis (AS) is a common inflammatory rheumatic disease. Mediterranean fever (MEFV) gene, which has already been identified as being responsible for familial Mediterranean fever (FMF), is also a suspicious gene for AS because of the clinical association of these two diseases. The aim of this study was to explore the frequency and clinical significance ofMEFVgene mutations (M694V, M680I, V726A, E148Q and P369S) in a cohort of Turkish patients with AS. Genomic DNAs of 103 AS patients and 120 controls were isolated and genotyped using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) methods. There was a statistically significant difference of theMEFVgene mutation carrier rates between AS patients and healthy controls (p= 0.004, OR: 2.5, 95% CI: 1.32–4.76). This association was also observed in allele frequencies (p= 0.005, OR: 2.3, 95% CI: 1.27–4.2). A relatively higher frequency was observed for M694V mutation in AS patients than controls (10.7% versus 4.2% ,p= 0.060). There were no significant differences between MEFV mutation carriers and non-carriers with respect to the clinical and demographic characteristics. The results of this study suggest thatMEFVgene mutations are positively associated with a predisposition to develop AS.

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Increased frequency of MEFV genes in patients with epigastric pain syndrome

Balkan Journal of Medical Genetics ◽

10.1515/bjmg-2017-0020 ◽

2017 ◽

Vol 20 (2) ◽

pp. 51-58 ◽

Cited By ~ 2

Author(s):

BD Coskun ◽

A Kiraz ◽

E Sevinc ◽

O Baspinar ◽

E Cakmak

Keyword(s):

Epigastric Pain ◽

Gene Mutations ◽

Pain Syndrome ◽

Turkish Population ◽

Heterozygous Mutation ◽

Epigastric Pain Syndrome ◽

History Of ◽

High Risk Populations ◽

Mediterranean Fever ◽

Colchicine Therapy

Abstract Atypical clinical forms of familial Mediterranean fever (FMF) can be misdiagnosed as therapy-resistant epigastric pain syndrome (EPS) for they share many of the same clinical features, such as abdominal pain. Thus, we aimed to determined the frequency of FMF in patients who were followed with a diagnosis of therapy-resistant EPS. Seventy-five patients with therapy-resistant EPS and 20 controls were involved in the study. To detect the FMF in patients with therapy-resistant EPS, Tel-Hashomer criteria, family history of FMF were researched and recorded. We performed performed MEFV gene analysis on all patients. Forty-three patients with EPS (57.3%) had MEFV gene mutations and the carrier rate was 30.0%. The most common MEFV gene alteration was R202Q (55.8%), followed by E148Q (16.2%), R761H (16.2%), V726A (9.3%), M680I (9.3%) and M694V (4.6%). Rarely seen mutations in the Turkish population were also identified: K695R (2.3%), L110P (2.3%) and G304R (2.3%). Eight patients with EPS were diagnosed with FMF and started on colchicine therapy. Three patients with compound heterozygosities for three mutations, two patients with compound heterozygosities for two mutations (K695R/ V726A and R202Q/ R761H), one patient with homozygous R202Q, one patient with heterozygous R202Q mutation and one patient with non- R202Q heterozygous mutation (G304R/–) had clinical FMF symptoms and were started on colchicine therapy. Patients who have therapy-resistant EPS should also be questioned about FMF, especially in high risk populations.

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MEFV gene mutations in Iranian patients with familial mediterranean fever (FMF)

The American Journal of Gastroenterology ◽

10.1016/s0002-9270(03)00980-8 ◽

2003 ◽

Vol 98 (9) ◽

pp. S72-S73 ◽

Cited By ~ 1

Author(s):

M ZALI

Keyword(s):

Familial Mediterranean Fever ◽

Mefv Gene ◽

Gene Mutations ◽

Mediterranean Fever ◽

Iranian Patients

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Transmigration of Neutrophils From Patients With Familial Mediterranean Fever Causes Increased Cell Activation

Frontiers in Immunology ◽

10.3389/fimmu.2021.672728 ◽

2021 ◽

Vol 12 ◽

Author(s):

Anush Martirosyan ◽

David Poghosyan ◽

Susanna Ghonyan ◽

Nune Mkrtchyan ◽

Gayane Amaryan ◽

...

Keyword(s):

Familial Mediterranean Fever ◽

Cell Size ◽

Actin Polymerization ◽

Cell Activation ◽

Gene Mutations ◽

Polymorphonuclear Neutrophils ◽

Cytoskeletal Dynamics ◽

Intracellular Expression ◽

Aged Cell ◽

Mediterranean Fever

Familial Mediterranean fever (FMF) is caused by pyrin-encoding MEFV gene mutations and characterized by the self-limiting periods of intense inflammation, which are mainly mediated by a massive influx of polymorphonuclear neutrophils (PMNs) into the inflamed sites. Perturbation of actin polymerization by different pathogens was shown to activate the pyrin inflammasome. Our aim was to test whether cytoskeletal dynamics in the absence of pathogens may cause abnormal activation of PMNs from FMF patients. We also aimed to characterize immunophenotypes of circulating neutrophils and their functional activity. Circulating PMNs displayed heterogeneity in terms of cell size, granularity and immunophenotypes. Particularly, PMNs from the patients in acute flares (FMF-A) exhibited a characteristic of aged/activated cells (small cell size and granularity, up-regulated CXCR4), while PMNs form the patients in remission period (FMF-R) displayed mixed fresh/aged cell characteristics (normal cell size and granularity, up-regulated CD11b, CD49d, CXCR4, and CD62L). The findings may suggest that sterile tissue-infiltrated PMNs undergo reverse migration back to bone marrow and may explain why these PMNs do not cause immune-mediated tissue damage. A multidirectional expression of FcγRs on neutrophils during acute flares was also noteworthy: up-regulation of FcγRI and down-regulation of FcγRII/FcγRIII. We also observed spontaneous and fMPL-induced activation of PMNs from the patients after transmigration through inserts as seen by the increased expression of CD11b and intracellular expression of IL-1β. Our study suggests heightened sensitivity of mutated pyrin inflammasome towards cytoskeletal modifications in the absence of pathogens.

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Frequency and Disease Severity of Familial Mediterranean Fever (FMF) Related MEFV Gene Mutations Among Ankylosing Spondylitis Patients

Turkiye Klinikleri Journal of Medical Sciences ◽

10.5336/medsci.2013-34490 ◽

2014 ◽

Vol 34 (2) ◽

pp. 223-230 ◽

Cited By ~ 2

Author(s):

Aslı TUFAN ◽

Sibel Zehra AYDIN ◽

Fatih EREN ◽

Pamir ATAGÜNDÜZ

Keyword(s):

Ankylosing Spondylitis ◽

Familial Mediterranean Fever ◽

Disease Severity ◽

Mefv Gene ◽

Gene Mutations ◽

Mediterranean Fever

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Two cases of periodic fever syndrome with coexistent mevalonate kinase and mediterranean fever gene mutations

The Turkish Journal of Pediatrics ◽

10.24953/turkjped.2017.04.015 ◽

2017 ◽

Vol 59 (4) ◽

pp. 467 ◽

Cited By ~ 1

Author(s):

Mustafa Çakan ◽

Nuray Aktay-Ayaz ◽

Gonca Keskindemirci ◽

Şerife Gül Karadağ

Keyword(s):

Periodic Fever ◽

Gene Mutations ◽

Mevalonate Kinase ◽

Periodic Fever Syndrome ◽

Mediterranean Fever

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The Frequency of Familial Mediterranean Fever Gene Mutations and the Correlations between Phenotype and Genotype in Turkish Children

Asian Journal of Pediatric Research ◽

10.9734/ajpr/2020/v4i230145 ◽

2020 ◽

pp. 20-26

Author(s):

Hakan Erdogan ◽

Ayse Cavidan Sonkur ◽

Orhan Görükmez ◽

Ayse Erdogan ◽

Dilek Damla Saymazlar ◽

...

Keyword(s):

Familial Mediterranean Fever ◽

Mutation Screening ◽

Mefv Gene ◽

Gene Mutations ◽

Retrospective Case ◽

Turkish Children ◽

Pathogenic Variants ◽

Frequent Mutations ◽

Training And Research ◽

Mediterranean Fever

Aim: Familial Mediterranian Fever is an autosomal recessive disease characterized by recurrent inflammatory attacks of serosal membranes. The aim of the current study was to determine the frequency of the Mediterranean fever (MEFV) gene pathogenic variants in 158 children (78 male, 80 female) diagnosed with Familial Mediterranean Fever (FMF) and to compare the phenotype-genotype correlation. Methods: In our retrospective case-control study, 158 FMF patients (78 males, 80 females) who were diagnosed with MEFV gene mutation in Bursa Yuksek Ihtisas Training and Research Hospital, Department of Pediatrics between January 2018 and June 2019 were included in the study. Mutation screening of the MEFV gene was performed for 12 mutations and the 8 most common mutations were taken into the study. Results: Abdominal pain (77.8%), fever (74%) and arthralgia (46.2%) were the most prevalent clinical features in our patients. The most frequent mutations were M694V, E148Q, V726A, M680I and P369S. In cases with M694 mutation, it was noted that the incidence of arthritis was 2.5 times, appendectomy frequency 3.1 times higher, and early diagnosis probability 3.2 times higher. The frequency of chest pain was 2.9 times higher in the M680I mutation, and the frequency of arthralgia was 2.2 times higher in the P369S mutation. Conclusion: Patient’s mutations in FMF patients are important for clinical expectations, and some mutations such as P369S are not as innocent as expected. However, reevaluation of phenotypes of mutations that are rare with more patients will be significant.

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Periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome, Hodgkin's lymphoma,and the familial Mediterranean fever gene

Case Reports in Internal Medicine ◽

10.5430/crim.v1n1p37 ◽

2014 ◽

Vol 1 (1) ◽

pp. 37

Author(s):

Ala Atamna ◽

Corina Hershkovici ◽

Avishay Elis

Keyword(s):

Familial Mediterranean Fever ◽

Hodgkin’S Lymphoma ◽

Periodic Fever ◽

Gene Mutations ◽

Aphthous Stomatitis ◽

High Rate ◽

Hodgkin's Lymphoma ◽

Inflammatory Disorder ◽

Mediterranean Fever ◽

Pfapa Syndrome

The syndrome of periodic fever, aphthous stomatitis, pharyngitis, and adenopathy (PFAPA) is a benign, self-limited, auto-inflammatory disorder. The attacks usually start at age 2 to 5 years and cease before the age of 10 years. Affected children grow and develop normally and experience no long-term sequelae. The course of PFAPA syndrome is attenuated by the carrier state of the familial Mediterranean fever (FMF) gene, MEFV. A high rate of MEFV mutations has also been reported in various hemato-lymphoid neoplasms. We describe a 19-year-old woman with PFAPA syndrome in remission who was diagnosed with Hodgkin's lymphoma. Although mutations in the FMF gene were not found in this case, the association of PFAPA syndrome with FMF gene mutations and hematological malignancies is discussed.

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