Adaptation to Mediterranea

The Mediterranean region encompasses countries that surround Mediterranean Sea. Due to its position at the intersection of Eurasia and Africa it has often been a route of human migrations during history, which contributed to its high biodiversity. People living in this area had been exposed to the episodes of natural selection that led to the establishment of specific genetic variations, for which is thought to carry a certain adaptation. Some recent studies have shown that genetic adaptations are probably related to the immune defense against infectious pathogens. One of the most recognizable disease of the region is familial Mediterranean fever (FMF), a prototype of a monogenic autoinflammatory disease. FMF is predisposed by the mutations in the Mediterranean fever (MEFV) gene that encodes inflammasome regulatory protein - pyrin. Specific variations of several other genes have been proposed to confer a protection against Plasmodium malariae parasite. Some of these are hemoglobin S (HbS), thalassemia, glucose-6-phosphate dehydrogenase deficiency, ovalocytosis, and mutation in the Duffy antigen (FY). In this chapter we will summarize important genetics and pathogenesis features of diseases commonly encountered in the Mediterranean region with a short discussion of potential adaptations that they may carry.

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Kawasaki disease triggered by EBV virus in a child with Familial Mediterranean Fever

Italian Journal of Pediatrics ◽

10.1186/s13052-019-0717-8 ◽

2019 ◽

Vol 45 (1) ◽

Cited By ~ 2

Author(s):

Maria Cristina Maggio ◽

Carmelo Fabiano ◽

Giovanni Corsello

Keyword(s):

Kawasaki Disease ◽

Familial Mediterranean Fever ◽

Epstein Barr Virus ◽

Autoinflammatory Disease ◽

Mefv Gene ◽

Clinical Manifestations ◽

Epstein Barr Virus Infection ◽

Barr Virus ◽

Mediterranean Fever ◽

Epstein Barr

Abstract Background Familial Mediterranean Fever is a monogenic autoinflammatory disease, secondary to mutation of MEFV gene, and typically expressed with recurrent attacks of fever, serositis, rash, aphthous changes in lips and/or oral mucosa. Kawasaki Disease, an acute systemic vasculitis with persistent fever (5 or more days), rash, stomatitis, conjunctivitis, lymphadenopathy, changes in extremities, is currently considered a multifactorial autoinflammatory disease. An infection, as Epstein Barr virus, can be the trigger of Kawasaki Disease. Case presentation We describe the clinical case of a 3-year-old boy with Kawasaki disease. Successfully treated with intravenous immune globulin, acetyl salicylate acid, he late developed anaemia and thrombocytopenia. The Epstein-Barr virus infection has been demonstrated and he showed a resolution of the clinical manifestations of Kawasaki disease with the persistence of coronaritis, without aneurisms. However, for the personal and familial history of monthly recurrent attacks of fever, pharyngitis, abdominal pain, the genetic study of MEFV was performed and demonstrated 3 heterozygous mutations of MEFV (E148Q, P369S, R408Q). Conclusions Mutations of MEFV can contribute to increase inflammatory expression in other diseases, as Kawasaki disease.

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013. SUCCESSFUL USE OF TOCILIZUMAB IN TWO CASES OF SEVERE UNDEFINED AUTOINFLAMMATORY DISEASE WITH A SINGLE COPY OF THE MEDITERRANEAN FEVER GENE

Rheumatology ◽

10.1093/rheumatology/kex062.013 ◽

2017 ◽

Vol 56 (suppl_2) ◽

Author(s):

Elena Nikiphorou ◽

Vassos Neocleous ◽

Leonidas A. Phylactou ◽

Savvas Psarelis

Keyword(s):

Autoinflammatory Disease ◽

Single Copy ◽

Mediterranean Fever ◽

The Mediterranean

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R761H M694I, M694V, V726A, R202Q, M680I AND E148Q MEFV GENE (FAMILIAL MEDITERRANEAN FEVER GENE) MUTATIONS IN THE AZERBAIJANİAN PATİENTS

Ambiance in Life International Scientific Journal in Medicine of Southern Caucasus ◽

10.36962/0601202150 ◽

2021 ◽

Vol 06 (01) ◽

pp. 50-51

Author(s):

Huseynova Lala Huseynova Lala ◽

Huseynova Qumru Huseynova Qumru

Keyword(s):

Familial Mediterranean Fever ◽

Mediterranean Region ◽

Phenotypic Variability ◽

Mefv Gene ◽

Eastern Mediterranean Region ◽

Nucleotide Sequences ◽

Exon 2 ◽

Mediterranean Fever ◽

The Republic ◽

Exon 10

MEFV gene (Familial Mediterranean Fever Gene) is located on chromosome 16 - 16.13.3., and it is composed of 3,242,028-3,256,776 nucleotides. It is specified as having an autosome-recessive hereditary type. Autosome-dominant hereditary species were also recorded(2,4). The MEFV RoRet genes family contains exon 10, consisting of 10,000 nucleotide sequences(5). The length of the transcript consists of 3.7 thousand nucleotide sequences consisting of 761 synthesized pyridine protein amino acid bases(1,3) MEFV gene researches were performed in the population of the Republic of Azerbaijan. Over 80 mutations have been identiﬁed so far. Four missense mutations (M680I, M694V, M694I, and V726A) in exon 10, together with E148Q in exon 2, account for the majority of FMF mutations in populations originating from areas around the eastern Mediterranean region. The various combinations of MEFV mutations are largely associated with the phenotypic variability of the disease. The most serious complication of FMF is the development of renal amyloidosis, which may be the only manifestation of the disease. The molecular-genetic study of the MEFV gene isolated from the genome DNA of 18 patients suspected of Family Disease Fever has identified 7 mutations: R761H M694I, M694V, V726A, R202Q, M680I and E148Q. All patients were of Azerbaijan origin, from the Mediterranean region of Azerbaijan. They were evaluated for clinical findings and family history of FMF. Seven mutations of MEFV gene were identified in heterozygous, homozygous and compound conditions: R761H M694I, M694V, V726A, R202Q, M680I and E148Q. The mutations E148Q and R202Q were discovered in exon 2 and R761H M694I, M694V, V726A, M680I were found in exon10 in the population of the Republic of Azerbaijan.

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Successful use of tocilizumab in two cases of severe autoinflammatory disease with a single copy of the Mediterranean fever gene

Rheumatology ◽

10.1093/rheumatology/kex180 ◽

2017 ◽

Vol 56 (9) ◽

pp. 1627-1628 ◽

Cited By ~ 3

Author(s):

Elena Nikiphorou ◽

Vassos Neocleous ◽

Leonidas A. Phylactou ◽

Savvas Psarelis

Keyword(s):

Autoinflammatory Disease ◽

Single Copy ◽

Mediterranean Fever ◽

The Mediterranean

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SIMILARITIES AND DIFFERENCES BETWEEN FAMILIAL MEDITERRANEAN FEVER AND BEHÇET’S DISEASE

Central Asian Journal of Medical Hypotheses and Ethics ◽

10.47316/cajmhe.2021.2.1.07 ◽

2021 ◽

Vol 2 (1) ◽

pp. 43-50

Author(s):

Ummusen Kaya Akca ◽

Ezgi Deniz Batu

Keyword(s):

Familial Mediterranean Fever ◽

Behçet’S Disease ◽

Behcet’S Disease ◽

Behçet's Disease ◽

Mefv Gene ◽

Common Symptom ◽

Behcet's Disease ◽

Mediterranean Fever ◽

Similarities And Differences ◽

The Mediterranean

Familial Mediterranean Fever (FMF) is the most common monogenic autoinflammatory disease, mainly affecting populations originating from the Eastern Mediterranean region. Behçet’s Disease (BD) is grouped in polygenic autoinflammatory diseases. It is a systemic vasculitis that affects all types and sizes of blood vessels. The aim of this article is to shed light on similarities and differences between FMF and BD. BD is frequently reported along the ancient Silk Road, extending from the Far East to the Mediterranean basin. Several studies have searched for the association between FMF and BD. FMF is caused by mutations of the MEditerranean FeVer (MEFV) gene while an increased frequency of MEFV mutations is reported in BD patients. Although BD and FMF share some epidemiological and pathophysiological features, there are distinct clinical characteristics of these nosological entities. Mucocutaneous manifestations, especially recurrent oral ulcers, are the most common symptom in BD patients whereas fever accompanied by serosal inflammation is the main clinical presentation in FMF patients.

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The spectrum of MEFV gene mutations and genotype-phenotype correlation in Egyptian patients with familial Mediterranean fever

International Journal of Research in Medical Sciences ◽

10.18203/2320-6012.ijrms20171233 ◽

2017 ◽

Vol 5 (4) ◽

pp. 1388 ◽

Cited By ~ 1

Author(s):

Fahmy T. Ali ◽

Mostafa M. Elhady ◽

Hanan H. Abbas ◽

AbdAllah Y. Mandouh

Keyword(s):

Familial Mediterranean Fever ◽

Mefv Gene ◽

Gene Mutations ◽

Compound Heterozygous ◽

Homozygous Mutation ◽

Clinical Criteria ◽

Egyptian Patients ◽

Mediterranean Fever ◽

The Mediterranean ◽

Severity Of The Disease

Background: Familial Mediterranean fever (FMF) is an autosomal recessive disease mainly affecting subjects of the Mediterranean origin. It is an auto-inflammatory periodic disorder that is caused by mutations in the Mediterranean fever gene (MEFV) located on chromosome 16.Methods: The current study was designed to assess the prevalence and frequency of different MEFV gene mutations among 104 FMF clinically diagnosed Egyptian patients and to evaluate the change extent in the values of some biochemical markers (ESR, CRP, Fibrinogen-C, SAA and IL1) in different participants with different FMF severity scores.Results: According to allele status 28 patients (27%) were homozygous mutation carriers, 38 (36.5%) were with compound heterozygous mutations and 38 (36.5%) were identified as heterozygous for one of the studied mutations. Of the studied mutations, M694I, E148Q, V726A, M680I, and M694V accounted for 28.1%, 26.8%, 16.9%, and 11.3% of mutations respectively. The R761H and P369S mutations were rarely encountered mutations (1.4%). The clinical features with M694I were associated with more severe clinical course. There is a drastic elevation in the levels of estimated parameters as their levels were increased as long as the severity of the disease increased.Conclusions: The diagnosis of FMF cannot be performed on the basis of genetic testing or clinical criteria alone. So, we recommended the combination between clinical and molecular profiling for FMF diagnosis and scoring.

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In Silico Prediction of the Deleterious Effect of a Mutation: Proceed with Caution in Clinical Genetics

Clinical Chemistry ◽

10.1373/clinchem.2004.036053 ◽

2004 ◽

Vol 50 (11) ◽

pp. 1974-1978 ◽

Cited By ~ 74

Author(s):

Dimitri Tchernitchko ◽

Michel Goossens ◽

Henri Wajcman

Keyword(s):

Deleterious Effect ◽

Sequence Variation ◽

Mefv Gene ◽

Tumor Necrosis Factor Receptor ◽

Point Of View ◽

Experimental Investigations ◽

Clinical Genetics ◽

Tnfrsf1a Gene ◽

Mediterranean Fever ◽

Glucose 6 Phosphate Dehydrogenase

Abstract When a sequence variation is found in a candidate gene for a disease, it is important to establish whether this change is neutral or responsible for the observed disorders in a patient. To answer this question, in the absence of further experimental investigations, several simulation programs have been proposed to predict whether a nonsynonymous single-nucleotide polymorphism is likely to have or not have a deleterious effect on the phenotype. In this work, we tested two such programs, PolyPhen and SIFT, using two kinds of targets. The first ones concerned the products of the hemoglobin and glucose-6-phosphate dehydrogenase genes, which are abundantly documented. The second concerned two systems for which much less information is available: (a) the TNFRSF1A gene, implicated in tumor necrosis factor receptor-associated periodic syndrome, and (b) the MEFV gene, which is believed to be involved in familial Mediterranean fever. Our data suggest that, from a practical point of view, these programs should not be used to decide, in the absence of other tests or arguments, whether the sequence variation found in a patient is or is not responsible for the disease. The consequence of an erroneous prediction may be disastrous in the perspective of genetic counseling.

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Familial Mediterranean fever, from pathogenesis to treatment: a contemporary review

TURKISH JOURNAL OF MEDICAL SCIENCES ◽

10.3906/sag-2008-11 ◽

2020 ◽

Vol 50 (7) ◽

pp. 1591-1610 ◽

Cited By ~ 1

Author(s):

Abdurrahman TUFAN ◽

Helen J LACHMANN

Keyword(s):

Familial Mediterranean Fever ◽

Mefv Gene ◽

Regulatory Protein ◽

Degenerative Diseases ◽

New Developments ◽

Functional Assays ◽

Inflammatory Conditions ◽

New Gene ◽

Mediterranean Fever ◽

Generation Sequencing

Familial Mediterranean fever (FMF) (OMIM #249100) is the most common hereditary autoinflammatory disease in the world. FMF is caused by gain of function mutations of MEFV gene which encodes an immune regulatory protein, pyrin. Over the last few years, we have witnessed several new developments in the pathogenesis, genetic testing, diagnosis, comorbidities, disease related damage and treatment approaches to FMF. Elucidation of some of the pathogenic mechanisms has led to the discovery of pathways involved in inflammatory, metabolic, cardiovascular and degenerative diseases. The use of next generation sequencing in FMF has revealed many new gene variants whose clinical significance may be clarified by developing functional assays and biomarkers. Clinically, although FMF is considered an episodic disease characterized by brief attacks, recent systematic studies have defined several associated chronic inflammatory conditions. Colchicine is the mainstay of FMF treatment, and interleukin (IL)-1 antagonists are the treatment of choice in refractory or intolerant cases. Experience of IL-1 antagonists, anakinra and canakinumab, is now available in thousands of colchicine resistant or intolerant FMF patients. In this contemporary review, we surveyed current FMF knowledge in the light of these recent advances.

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