The regulation of MEFV expression and its role in health and familial Mediterranean fever

Grandemange, Sylvie; Aksentijevich, Ivona; Jéru, Isabelle; Gül, Ahmet; Touitou, Isabelle

doi:10.1038/gene.2011.53

Cited by 40 publications

(29 citation statements)

References 37 publications

(39 reference statements)

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“…Pyrin proteininin IL-1β işlenmesini engellemesi ve makrofaj apoptozuna izin vermesi, fonksiyonel olarak antienflamatuvar bir molekül olduğunu göstermektedir. Bu mekanizmaların bir sonucu olarak klinik tablo yüksek ateş ve sınırlı enflamasyon atakları ile seyreder (2,7,8). AAA hastaları tekrarlayan ve görünüşte sebepsiz olduğu düşünülen ancak sıklıkla artrit, peritonit, plörit ve bölgesel erizipel benzeri eritemlerle ilişkili olabilen yüksek ateşten muzdarip olurlar.…”

Section: Introductionunclassified

“…AAA hastaları tekrarlayan ve görünüşte sebepsiz olduğu düşünülen ancak sıklıkla artrit, peritonit, plörit ve bölgesel erizipel benzeri eritemlerle ilişkili olabilen yüksek ateşten muzdarip olurlar. Bu ataklar genellikle 12-72 saat sürer ve bu enflamatuvar reaksiyon polimorf nüveli lökositlerin etkilenmiş dokular içerisine akını ile karakterizedir (8). Halen AAA tanısı için kullanılmakta olan spesifik bir laboratuvar testi bulunmamaktadır.…”

Section: Introductionunclassified

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Molecular Diagnosis Experience in Familial Mediterranean Fever: The Most Frequent Mutations in the MEFV Gene

Çoşkunpınar¹,

Özvarnali²,

Çefle³

et al. 2018

Haseki

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ÖzAmaç: Ailevi Akdeniz Ateşi (AAA) tarihsel olarak en eski ve en yaygın otozomal resesif geçişli otoenflamatuvar hastalıktır. Bilinen bir patojen ya da otoantikoru bulunmamaktadır. Hastalık karın ağrısı ve ateş hecmeleriyle manifest olmaktadır ve bu dönemler "atak dönemi" olarak adlandırılır. Çalışmamızda AAA hastalığında, MEFV geni üzerinde, Türk toplumunda en sık mutasyona uğrayan bölgelerin tespiti amaçlandı.Yöntemler: Çalışmaya toplam 1840 ön tanılı olgu dahil edildi. Periferik kandan kit protokolüne uygun olarak DNA izole edildi. MEFV genindeki 22 hedef bölge polimeraz zincir reaksiyonu metodu ile çoğaltıldı. Pyrosequencing metodu ile hedef bölge gen dizinlemesi yapıldı. Bulgular: Hastalar yaş gruplarına göre iki gruba ayrılarak incelendiğinde <18 yaş grubunda yer alan 866 (454 kadın ve 412 erkek) hastanın ortalama yaşları 8,5±7,5'dir. Bu grupta yer alan hastalardan 547'sinde AAA ile ilişkilendirilen bir mutasyon saptanmadı. ≥18 yaş grubunda yer alan 974 (605 kadın ve 369 erkek) hastanın ortalama yaşları 35,4±12,5'dir. Bu grupta yer alan hastalardan 477'sinde AAA ile ilişkilendirilen bir mutasyona rastlanmadı.Sonuç: Tıbbi genetik bilim dalına 2014-2016 yılları arasında AAA ön tanısı ile gelen 781 erkek ve 1059 kadın olmak üzere toplam 1840 olgu MEFV geni üzerinde lokalize 22 ayrı mutasyon açısından analiz edildi. Bulgularımızın analizi elde edilen verilerin daha önceki Türk toplumuna ilişkin çalışmalarla uyumlu olduğunu göstermiştir. AnahtarSözcükler:Ailevi Akdeniz Ateşi, MEFV geni, pyrosequencing, mutasyonAim: Familial Mediterranean Fever (FMF) is the most frequent and historically the oldest autosomal recessive autoinflammatory disorder. No pathogen or auto-antibody has been shown to be associated with FMF. The disorder manifests with bouts of fever and abdominal pain, which are called "attacks". In the present study, we aimed to find the most frequent mutations in the MEFV gene in the Turkish population.Methods:Thousand eight hundred and forty patients with an initial diagnosis of FMF were enrolled in the study. DNA was extracted from the peripheral blood according to the kit protocol. Twenty-two target sequences of the MEFV gene were amplified with polimeraze chain reaction and sequenced with the pyrosequencing method.Results: When the patients were divided into two groups according to age, the mean age of 866 patients was 8.5±7.5 years in <18 age group, and that of 974 patients was 35.4±12.5 years in ≥18 age group. No mutations associated with FMF were found in 547 of patients in <18 age and 479 of the patients in ≥18 age groups. Conclusion:In the present study, we evaluated the frequency of 22 mutations in MEFV in 1840 patients, who had been admitted to the medical genetics division between the years 2014 and 2016 with an initial diagnosis of FMF. Analysis of our findings showed that our data are in agreement with previous publications concerning Turkish population.

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Section: Introductionunclassified

Molecular Diagnosis Experience in Familial Mediterranean Fever: The Most Frequent Mutations in the MEFV Gene

Çoşkunpınar¹,

Özvarnali²,

Çefle³

et al. 2018

Haseki

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“…It is an autoinflammatory disease characterized by recurrent, self-limited attacks of fever and inflammation of serosal surfaces. Pyrin is expressed mainly in neutrophils and macrophages, and modulates the production of the potent pro-inflammatory cytokine interleukin-1β through regulation of nuclear factor-κB and caspase-1 [2]. Neutrophil degranulation and release of proteases and other cytotoxic mediators can cause tissue damage.…”

Section: Objectivementioning

confidence: 99%

Urine Matrix Metalloproteinase-3 Level as a Biomarker for Monitoring in Familial Mediterranean Fever Attacks

Sözeri¹

2014

J Nephrol Ther

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Objective: Matrix metalloproteinase-3 (MMP-3) has been implicated in experimental and clinical models of human inflammatory conditions. Increased MMPs levels have been shown in serum and body fluids in inflammatory conditions. Familial Mediterranean Fever (FMF) is an inherited, auto inflammatory disease characterized by recurrent self-limited bouts of fever and localized inflammation. We aimed to investigate whether urine MMP-3 level can serve as a biomarker for monitoring attack in FMF patients in daily practice. Methods:We studied 50 patients diagnosed with FMF according to Tel Hashomer criteria and 32 age-matched healthy controls. We determined all subjects both in attack (FMF-AP) and attack free period (FMF-AFP) groups. Serum and urine samples were obtained within the first 6-24 h of the AP, and 10 days later after the attack (AFP). The serum samples were measured on the same day while urine samples were frozen immediately and stored at -80°C. Results:The mean age at onset was 57.26 ± 33.5 months. The most common symptoms seen during the attacks were: fever (80%) abdominal pain (72%), arthritis (40%). In genotype distribution, homozygous M694V mutation was seen mostly (28%). During AP, urine MMP-3 levels of patients were higher as well as during AFP and controls (2.32 ± 0.51, 0.89 ± 2.29 ng/mL and 1.24 ± 0.17 ng/mL, respectively, p=0.00). In AP, urinary MMP levels were higher in patients with arthritis than others (p<0.05). Urinary MMP-3 levels were also significantly higher in males (2.29 ± 0.45 versus 2.24 ± 0.57, p=0, 00). The patients with M694V allele (n=29) had statistically significant high urine MMP-3 levels than others (2.37 ± 0.56 versus 1.99 ± 0.31, p=0.04, respectively). Also, acute phase reactants were higher in patients with M694V allele without statistically significant difference (p=0. 89, 0.75, 0.86, 0.85, 0.7, respectively). Conclusion:In this study we focused on presence of MMPs in urine and showed inflammation-specific MMP patterns may provide clinicians valuable information in FMF patients.

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“…Das MEFV-Gen befindet sich auf Chromosom 16 und kodiert ein Protein − Pyrin − mit einer Länge von 781 Aminosäuren in 10 Exons [8]. Pyrin wird hauptsächlich in den klassischerweise dem angeborenen Immunsystem zugerechneten Zellen, d. h. in neutrophilen Granulozyten und Monozyten, exprimiert [9].…”

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“…Zusätzlich konnte eine Expression in peritonealen Fibroblasten nachgewiesen werden [10]. Durch Sequenz-und Strukturanalysen wurde eine neue Proteindomäne PYD ("PYrin Domain") im Bereich der N-terminalen Aminosäuren von Pyrin identifiziert [8]. Diese Domäne konnte in einer Reihe weiterer Proteine nachgewiesen werden, die eine wichtige Rolle für die Initiierung von Entzündungsprozessen spielen.…”

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Das familiäre Mittelmeerfieber

Paschke¹,

Beil²,

Ben-Chétrit³

2013

Gastroenterologie up2date

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Einleitung Das familiäre Mittelmeerfieber (FMF) ist eine monogenetische Erkrankung, die durch Punktmutationen des für das Protein Pyrin kodierenden Gens MEFV verursacht wird. Es ist durch rezidivierende, selbstlimitierende Fieberschübe mit Peritonitis, Pleuritis, Arthritis und erysipelähnlichen Hautveränderungen charakterisiert [1]. Das FMF ist der epidemiologisch wichtigste Vertreter der Gruppe der hereditären Autoinflammationssyndrome, die durch genetische Veränderungen von Regulatoren des angeborenen Immunsystems hervorgerufen werden [2]. Die Namensgebung geht auf die hohe Prävalenz des FMF in den ethnischen Gruppen des östlichen Mittelmeerraums zurück. In der Vergangenheit führte die medikamentös nicht kontrollierbare chronisch-rezidivierende Entzündung häufig zu einer Amyloidose mit Nierenversagen in der 4. Lebensdekade. Dieser Verlauf kann bei rechtzeitiger Diagnosestellung und Einleitung einer Behandlung mit Colchicin zur Anfallsprävention verhindert werden. Epidemiologie Die weltweit höchste Prävalenz findet sich in der Umgebung des östlichen Mittelmeeres. Sie variiert zwischen 1 : 400 in einigen Regionen der Türkei, 1 : 500 in Armenien und ca. 1 : 1000 in Israel [3]. Hinsichtlich der 3 häufigsten Mutationen wird ein Gründereffekt ("founder effect") vermutet, der auf Mutationsereignisse vor ungefähr 2500 Jahren in Mesopotamien zurück-zuführen sein könnte [3, 4]. Patienten mit FMF wurden auch in anderen Regionen identifiziert. So wird die Gesamtzahl der FMF-Patienten in Japan auf 300 geschätzt [5]. In Deutschland hat die überwiegende Zahl der Patienten mit FMF einen Migrationshintergrund. Ungefähr ¾ der Patienten haben türkischstäm-mige Vorfahren [6]. Das familiäre Mittelmeerfieber ist eine monogen vererbte Erkrankung, die am häufigsten in den ethnischen Gruppen des östlichen Mittelmeerraums zu finden ist. Ätiologie und Pathogenese Das FMF gehört zur Gruppe der periodischen Fiebersyndrome, die durch genetische Veränderungen von regulatorischen Proteinen des angeborenen Immunsystems charakterisiert sind [2]. Diese Erkrankungen werden auch als hereditäre Autoinflammationssyndrome bezeichnet und grenzen sich von den Autoimmunerkrankungen dadurch ab, dass keine krankheitstypischen autoreaktiven T-Zellen oder Antikörper nachweisbar sind.

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The regulation of MEFV expression and its role in health and familial Mediterranean fever

Cited by 40 publications

References 37 publications

Molecular Diagnosis Experience in Familial Mediterranean Fever: The Most Frequent Mutations in the MEFV Gene

Molecular Diagnosis Experience in Familial Mediterranean Fever: The Most Frequent Mutations in the MEFV Gene

Urine Matrix Metalloproteinase-3 Level as a Biomarker for Monitoring in Familial Mediterranean Fever Attacks

Das familiäre Mittelmeerfieber

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