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Serge Amselem - One of the best experts on this subject based on the ideXlab platform.
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A heterozygous variant in MEFV in a familial autoinflammatory syndrome with PAPA-like features
Pediatric Rheumatology, 2015Co-Authors: I Jéru, Serge Amselem, L Van Eyck, Vasiliki Lagou, J Ruuth-praz, Bruno Copin, Emmanuelle Cochet, Adrian Liston, An Goris, Carine WoutersAbstract:Autoinflammatory disorders are a group of diseases whose nosology and etiology are only partly understood. Among Mendelian forms, familial Mediterranean fever (FMF), due to mutations in MEFV, is one of the most frequent. Most MEFV mutations are located in exon 10 and are usually associated with an autosomal recessive mode of inheritance. MEFV encodes pyrin, which interacts with PSTPIP1, a protein involved in the rare autosomal dominant pyogenic arthritis, pyoderma gangrenosum and acne (PAPA) syndrome.
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MEFV analysis is of particularly weak diagnostic value for recurrent fevers in western european caucasian patients
Arthritis & Rheumatism, 2005Co-Authors: Dimitri Tchernitchko, S Moutereau, Marie Legendre, Andree Delahaye, Cecile Cazeneuve, C Lacombe, G Grateau, Serge AmselemAbstract:Objective Familial Mediterranean fever (FMF) is an autosomal-recessive disorder characterized by recurrent attacks of fever, with abdominal, thoracic, or articular pain. FMF is particularly common in Mediterranean populations, while other populations are rarely affected. MEFV gene analysis provides the only objective diagnostic criterion for FMF. However, the spectrum of MEFV mutations, which was first established in classically affected populations, remains insufficiently studied in other populations. The purpose of this study was to assess involvement of MEFV in the phenotype of western European Caucasian patients with a clinical diagnosis of FMF. Methods Mutation analysis was performed in 208 Caucasian patients from western Europe, by screening for the most common MEFV mutations in exons 2, 3, 5, and 10, and by sequencing the promoter region and the whole MEFV coding sequence in 21 of these patients. Results None of the patients carried 2 mutated alleles. Only 2 patients carried 1 mutated allele. Conclusion FMF-like syndromes in western European Caucasian populations cannot be explained by MEFV mutations. These results should be helpful in avoiding laborious and costly MEFV molecular analyses that, at the population level, seem to be of poor diagnostic value in the case of western European Caucasian patients, and rather should prompt a search for other causes in those patients.
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the tumor necrosis factor α dependent activation of the human mediterranean fever MEFV promoter is mediated by a synergistic interaction between c ebpβ and nfκb p65
Journal of Biological Chemistry, 2003Co-Authors: Stephanie Papin, Cecile Cazeneuve, Philippe Duquesnoy, Isabelle Jeru, Djillali Sahali, Serge AmselemAbstract:Abstract MEFV is a gene expressed specifically in myeloid cells and whose mutations underlie an autosomal recessive auto-inflammatory disease, called familial Mediterranean fever (FMF), characterized by recurrent episodes of serosal inflammation. This gene, which encodes a protein with unclear physiological functions, has been shown to be up-regulated by the pro-inflammatory cytokine tumor necrosis factor α (TNFα). However, the mechanism of this regulation is unknown, and the MEFV promoter is still to be characterized. Here, we show that 243 bp of the 5′-flanking region of the human MEFV gene are sufficient to direct high level expression of MEFV in TNFα-treated cells. The TNFα-induced expression of MEFV is dependent on both NFκB p65 and C/EBPβ that bind to evolutionarily conserved sites located, in the human promoter, at positions –163 and –55, respectively. As shown by a series of transcription and gel shift assays performed with wild-type and mutated promoter sequences, these two transcription factors act differently on the TNFα-dependent transcription of MEFV: C/EBPβ is the key regulatory factor required to confer cell responsiveness to TNFα, whereas NFκB p65 increases this response by means of a synergistic interaction with C/EBPβ that is dependent on the integrity of the identified –55 C/EBP binding site. Given the phenotype of patients with FMF, this C/EBP-NFκB interaction may represent a key step in the control of an inflammatory response that is abnormally high in this disease. These data, which shed novel light on the pathophysiology of FMF, represent an unusual example of cross-talk between C/EBP and NFκB pathways in TNFα signaling.
Aysin Bakkaloglu - One of the best experts on this subject based on the ideXlab platform.
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MEFV mutations in systemic onset juvenile idiopathic arthritis
Rheumatology, 2008Co-Authors: Nuray Aktay Ayaz, Seza Ozen, Engin Yilmaz, Nesrin Besbas, Yelda Bilginer, M Erguven, Ekim Z Taskiran, R Topaloglu, Aysin BakkalogluAbstract:OBJECTIVES: Autoinflammatory diseases constitute a large spectrum of monogenic diseases like FMF or cryopyrin-associated periodic syndromes (CAPS) and complex genetic trait diseases such as systemic onset juvenile idiopathic arthritis (SoJIA). An increased rate of MEFV mutations has been shown among patients with PAN and HSP, in populations where FMF is frequent. The aim of the study is to search for MEFV mutations in our patients with SoJIA and see whether these mutations had an effect on disease course or complications. METHODS: Thirty-five children with the diagnosis of SoJIA were screened for 12 MEFV mutations. The control data were obtained from a previous study of our centre determining the carrier frequency in Turkish population. RESULTS: Two patients were homozygous and three patients were heterozygous for the M694V mutation. One patient was a compound heterozygote for the M680I/V726A mutations. Heterozygous V726A mutation was found in one patient. The overall mutation frequency of patients was 14.28%. This figure had been compared with the previously published rate of disease-causing mutations in this country, which is 5%. Disease-causing mutations were found to be significantly more frequent in the SoJIA patients than the population (P < 0.01). Among these, M694V was the leading mutation with a frequency of 10% in SoJIA. Six patients carrying MEFV mutations were among the most resistant cases requiring biological therapy. CONCLUSION: SoJIA patients had a significantly higher frequency of MEFV mutations but clinical studies with large number of patients are needed to confirm the association of MEFV mutations with SoJIA and its course.
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prevalence of the MEFV gene mutations in childhood polyarteritis nodosa
The Journal of Pediatrics, 2007Co-Authors: Fatos Yalcinkaya, Birsin Z Ozcakar, Ozgur Kasapcopur, Aysenur Ozturk, Nejat Akar, Aysin Bakkaloglu, Nil Arisoy, Mesiha Ekim, Seza OzenAbstract:Objectives To test the hypothesis that alterations in the Mediterranean fever ( MEFV ) gene are a susceptibility factor for the development of polyarteritis nodosa (PAN) we investigated the prevalence of MEFV mutations in patients with PAN without any symptoms of familial Mediterranean fever (FMF). Study design Pediatric patients with PAN (n = 29) were enrolled in this study. Six predominant mutations (p.M694V, p.M680I, p.M694I, p.V726A, p.K695R, p.E148Q) in the MEFV gene were studied. Results Fifteen MEFV mutations were identified in 58 chromosomes. Eleven of the 29 patients (38%) were found to carry MEFV mutations. Three (10.3%) of them had homozygous p.M694V mutation, and one of the patients (3.4%) had compound heterozygous mutation (p.V726A/p.E148Q). Conclusions Our study confirms that alterations in the MEFV gene are important succeptibility factors for the development of PAN. We believe that mutations in MEFV gene provide a basis for the development of PAN both by forming a proinflammatory state and by possibly giving exaggerated response to streptococcal infections.
G Grateau - One of the best experts on this subject based on the ideXlab platform.
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MEFV analysis is of particularly weak diagnostic value for recurrent fevers in western european caucasian patients
Arthritis & Rheumatism, 2005Co-Authors: Dimitri Tchernitchko, S Moutereau, Marie Legendre, Andree Delahaye, Cecile Cazeneuve, C Lacombe, G Grateau, Serge AmselemAbstract:Objective Familial Mediterranean fever (FMF) is an autosomal-recessive disorder characterized by recurrent attacks of fever, with abdominal, thoracic, or articular pain. FMF is particularly common in Mediterranean populations, while other populations are rarely affected. MEFV gene analysis provides the only objective diagnostic criterion for FMF. However, the spectrum of MEFV mutations, which was first established in classically affected populations, remains insufficiently studied in other populations. The purpose of this study was to assess involvement of MEFV in the phenotype of western European Caucasian patients with a clinical diagnosis of FMF. Methods Mutation analysis was performed in 208 Caucasian patients from western Europe, by screening for the most common MEFV mutations in exons 2, 3, 5, and 10, and by sequencing the promoter region and the whole MEFV coding sequence in 21 of these patients. Results None of the patients carried 2 mutated alleles. Only 2 patients carried 1 mutated allele. Conclusion FMF-like syndromes in western European Caucasian populations cannot be explained by MEFV mutations. These results should be helpful in avoiding laborious and costly MEFV molecular analyses that, at the population level, seem to be of poor diagnostic value in the case of western European Caucasian patients, and rather should prompt a search for other causes in those patients.
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mutational spectrum in the MEFV and tnfrsf1a genes in patients suffering from aa amyloidosis and recurrent inflammatory attacks
Nephrology Dialysis Transplantation, 2002Co-Authors: Catherine Dode, Marc Delpech, Bouke P C Hazenberg, Christophe Pecheux, Daniel Cattan, Bruno Moulin, Anne Barthelemy, Marieclaire Gubler, G GrateauAbstract:Background. Among hereditary fevers characterized by recurrent attacks of fever and organ localized inflammation, familial Mediterranean fever (FMF), and tumour necrosis factor receptor superfamily 1A (TNFRSF1A) receptor associated periodic syndrome (TRAPS) are diseases with identified genes that can be associated with renal amyloidosis of the AA type. In this study we have characterized FMF and TRAPS genotypes in 38 unrelated patients suffering from amyloidosis AA and recurrent inflammatory attacks. Methods. Mutations of the MEFV and TNFRSF1A genes, responsible respectively for FMF and TRAPS, were searched for by amplifying, using polymerase chain reaction (PCR), genomic DNA, and direct sequencing. Results. Twenty-seven patients (71%) carried mutations in MEFV (22 patients with two mutations, two patients with a single mutation) or TNFRSF1A genes (three patients). Patients with MEFV mutations belonged to the classical at-risk ethnic group for FMF: Sephardic Jews, Turks, Armenians, and Arabs from the Maghreb. The main genotype encountered was M694VuM694V (19u22), one Turkish patient was M680I/M680I, and two Arab patients from the Maghreb were M694I/M694I. We found three Caucasian patients with the C55S, C70Y, R92Q mutations in the TNFRSF1A gene. Conclusions. In this series we observed that FMF is the main cause of AA amyloidosis in Sephardic Jews and Turks. MEFV and TNFRSF1A mutations were found in only 6 of 14 Arab patients from the Maghreb. We found three families (one Caucasian and two from Maghreb) with AA amyloidosis without MEFV or TNFRSF1A mutations, suggesting that other genetic cause(s) exist(s). The characterization of mutations in MEFV and TNFRSF1A is important for the therapeutic behaviour of AA amyloidosis associated with inherited recurrent fever.
Avi Livneh - One of the best experts on this subject based on the ideXlab platform.
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IS THERE A CORRELATION BETWEEN CARRIAGE OF AN MEFV MUTATION AND GOUT
Harefuah, 2019Co-Authors: Amit Druyan, Eitan Giat, Avi Livneh, Ron Kedem, Merav LidarAbstract:INTRODUCTION: Gout is an inflammatory condition mediated by Interleukin-1-beta (IL-1β). A mutation in the MEFV gene (the gene related to Familial Mediterranian fever) may cause an elevation in IL-1β, and is associated with a variety of inflammatory conditions. Reports in the literature are inconsistent as to whether a mutated MEFV gene is related to the phenotype of gout. OBJECTIVES: To assess whether a carriage state of a mutation in the MEFV gene correlates with the expression and severity of gout. METHODS: A total of 73 patients, 50 with gout and 23 with hyperuricemia were examined for an MEFV mutation. Carriage rate was compared between hyperuricemic and gout patients, and disease activity measures were compared between MEFV mutation carriers and non-carriers. RESULTS: We did not find a statistically significant difference in the carriage rate of an MEFV mutation between gout patients and hyperuricemic patients without gout, nor did we find a correlation between MEFV mutation carriage and gout severity. CONCLUSIONS: Further large-scale studies should be conducted in order to determine a possible correlation between MEFV mutation carriage and gout.
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Carriage of Mediterranean Fever (MEFV) Mutations in Patients with Postpericardiotomy Syndrome (PPS).
Israel Medical Association Journal, 2017Co-Authors: Ido-david Dechtman, Chagai Grossman, Yael Shinar, R Cohen, E. Nachum, Ehud Raanani, Avi LivnehAbstract:BACKGROUND: Postpericardiotomy syndrome (PPS) is characterized by pleuro-pericardial inflammation, which occurs in patients undergoing surgical procedures involving the pleura, pericardium, or both. The syndrome is considered to be immune mediated. However, its pathogenesis is not fully understood. It has previously been demonstrated that the Mediterranean Fever (MEFV) gene, which is associated with familial Mediterranean fever (FMF), has a role in the activation and expression of several inflammatory diseases. OBJECTIVES: To investigate whether carriage of the MEFV mutation may precipitate PPS or affect its phenotype. METHODS: The study population included 45 patients who underwent cardiac surgery and developed PPS. The control group was comprised of 41 patients who did not develop PPS. Clinical and demographic data was collected. The severity of PPS was evaluated. Genetic analysis to determine the carriage of one the three most common MEFV gene mutations (M694V, V726A, E148Q) was performed. The carriage rate of MEFV mutations in patients with and without PPS was compared. Association between MEFV mutation carriage and severity of PPS was evaluated. RESULTS: The rate of mutation carriage in the MEFV gene was similar in patients with and without PPS (15.6% in the study groups vs. 29.3% in the control group, P = 0.1937). The rate of mutation carriage in the MEFV gene was significantly lower among patients with severe PPS as compared to patients with mild-moderate PPS (4.8% vs. 25%, P < 0.05). CONCLUSIONS: Carriage of mutations in the MEFV gene is not associated with development of PPS; however, it may affect PPS severity.
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familial mediterranean fever without MEFV mutations a case control study
Orphanet Journal of Rare Diseases, 2015Co-Authors: Ilan Benzvi, Chagai Grossman, Corinne Herskovizh, Olga Kukuy, Yonatan Kassel, Avi LivnehAbstract:Although familial Mediterranean fever (FMF) was originally defined as an autosomal recessive disorder, approximately 10–20% of FMF patients do not carry any FMF gene (MEFV) mutations. Fine phenotype characterization may facilitate the elucidation of the genetic background of the so called “FMF without MEFV mutations”. In this study we clinically and demographically characterize this subset. MEFV mutation-negative FMF and control patients were recruited randomly from a cohort followed in a dedicated FMF clinic. The control subjects comprised 2 groups: 1. typical population of FMF, consisting of genetically heterogeneous patients manifesting the classical spectrum of FMF phenotype and 2. a severe phenotype of FMF, consisting of FMF patients homozygous for the p.M694V mutation. Forty-seven genetic-negative, 60 genetically heterogeneous and 57 p.M694V homozygous FMF patients were enrolled to the study. MEFV-mutation negative FMF patients showed a phenotype closely resembling that of the other 2 populations. It differed however from the p.M694V homozygous subset by its milder severity (using Mor et al. scoring method), as determined by the lower proportion of patients with chest and erysipelas like attacks, lower frequency of some of the chronic manifestations, lower colchicine dose and older age of disease onset. MEFV mutation-negative FMF by virtue of its classical FMF phenotype is probably associated with a genetic defect upstream or downstream to MEFV related metabolic pathway.
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familial mediterranean fever gene MEFV mutations as a modifier of systemic lupus erythematosus
Lupus, 2012Co-Authors: Yael Shinar, E Kosach, Pnina Langevitz, Gisele Zandmangoddard, R Pauzner, Einat Rabinovich, Avi LivnehAbstract:The objective of this study was to assess the prevalence of the Mediterranean FeVer (MEFV) gene mutations in systemic lupus erythematosus (SLE) patients and their effect on organ involvement, as well as disease activity and severity. The frequencies of three familial Mediterranean fever-related MEFV gene mutations (M694V, V726A and E148Q) were investigated in 70 SLE patients. Organ involvement, Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores were correlated with mutation carriage. Eleven of 70 patients (15.7%) were found to carry an MEFV mutation. A single patient harbored two mutations, E148Q and V726A, without overt familial Mediterranean fever while the rest were heterozygous carriers. Four of the 11 carried an M694V mutation, four carried V726A and two carried E148Q. The majority of MEFV mutation carriers were Sephardic while non-carriers were mainly of Ashkenazi origin ...
Nuray Aktay Ayaz - One of the best experts on this subject based on the ideXlab platform.
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The influence of carrying MEFV gene variants on juvenile systemic lupus erythematosus
Rheumatology International, 2019Co-Authors: Ayşe Tanatar, Betül Sözeri, Mustafa Çakan, Şerife Gül Karadağ, Ayşenur Paç Kısaarslan, Nuray Aktay AyazAbstract:Juvenile-onset systemic lupus erythematosus (jSLE) patients typically have a more severe disease course than adults with SLE. We aimed to assess the prevalence and disease course of jSLE patients carrying MEFV variants. MEFV variant analyses were performed in 44 jSLE patients and effect of these variants on disease severity and course was analyzed by SLEDAI score and SLICC/ACR index. Ten of the patients (22.7%) had a MEFV variant. The median (min–max) SLEDAI score and SLICC/ACR index were 2(0–13) and 0(0–3), respectively. Median age at disease onset, disease duration, SLICC/ACR indexes, SLEDAI scores, clinical and laboratory findings of the patients were comparable in carriers of variants and non-carriers. Nineteen patients (43.2%) had biopsy-proven lupus nephritis and four of these patients had MEFV variants. There was no significant difference between patients with and without MEFV carriers in terms of lupus nephritis. Even though not significant statistically, renal involvement was milder in MEFV carriers than non-carriers. The presence of MEFV variants does not increase the overall susceptibility to jSLE in our cohort, while larger number of patients is required to display the protective role of MEFV variants in jSLE.
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MEFV mutations in systemic onset juvenile idiopathic arthritis
Rheumatology, 2008Co-Authors: Nuray Aktay Ayaz, Seza Ozen, Engin Yilmaz, Nesrin Besbas, Yelda Bilginer, M Erguven, Ekim Z Taskiran, R Topaloglu, Aysin BakkalogluAbstract:OBJECTIVES: Autoinflammatory diseases constitute a large spectrum of monogenic diseases like FMF or cryopyrin-associated periodic syndromes (CAPS) and complex genetic trait diseases such as systemic onset juvenile idiopathic arthritis (SoJIA). An increased rate of MEFV mutations has been shown among patients with PAN and HSP, in populations where FMF is frequent. The aim of the study is to search for MEFV mutations in our patients with SoJIA and see whether these mutations had an effect on disease course or complications. METHODS: Thirty-five children with the diagnosis of SoJIA were screened for 12 MEFV mutations. The control data were obtained from a previous study of our centre determining the carrier frequency in Turkish population. RESULTS: Two patients were homozygous and three patients were heterozygous for the M694V mutation. One patient was a compound heterozygote for the M680I/V726A mutations. Heterozygous V726A mutation was found in one patient. The overall mutation frequency of patients was 14.28%. This figure had been compared with the previously published rate of disease-causing mutations in this country, which is 5%. Disease-causing mutations were found to be significantly more frequent in the SoJIA patients than the population (P < 0.01). Among these, M694V was the leading mutation with a frequency of 10% in SoJIA. Six patients carrying MEFV mutations were among the most resistant cases requiring biological therapy. CONCLUSION: SoJIA patients had a significantly higher frequency of MEFV mutations but clinical studies with large number of patients are needed to confirm the association of MEFV mutations with SoJIA and its course.
