Clinical impact of<i>MEFV</i>mutations in children with periodic fever in a prevalent western European Caucasian population

Federici, Silvia; Calcagno, G; Finetti, Martina; Gallizzi, Romina; Meini, Antonella; Vitale, Agata; Caroli, Francesco; Cattalini, Marco; Caorsi, Roberta; Zulian, Francesco; Tommasini, Alberto; Insalaco, Antonella; Sormani, Maria Pia; Baldi, Maurizia; Ceccherini, Isabella; Martini, Alberto; Gattorno, Marco

doi:10.1136/annrheumdis-2011-200977

Cited by 69 publications

(39 citation statements)

References 27 publications

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“…We have previously reported that the frequency of FMF-like symptoms decreases from patients carrying two high-penetrance mutations to patients with a single low-penetrance mutation 33. Analyses performed in single families in the present study support this concept.…”

Section: Resultssupporting

confidence: 84%

“…In conclusion, we have shown that MEFV -mutated monocytes are characterised by a mild state of stress and IL-1β oversecretion, which increase proportionally with the number and penetrance of mutations, thus supporting the dosage effect observed in animal models and clinical studies 20 33. In human monocytes, the presence of mutated pyrin is not sufficient to promote the LPS-mediated secretion of IL-1β independently of the activation of the NLRP3 inflammasome.…”

Section: Discussionsupporting

confidence: 64%

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Increased NLRP3-dependent interleukin 1β secretion in patients with familial Mediterranean fever: correlation withMEFVgenotype

et al. 2013

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MEFV-mutated monocytes display enhanced IL-1β secretion, which correlates with number of high-penetrance mutations and level of endogenous ROS. Unlike NLRP3-mutated cells, monocytes carrying MEFV mutations withstand oxidative stress and preserve IL-1Ra production, thereby limiting inflammation. Finally, in contrast with that found in the animal model, the increased secretion of IL-1β by LPS-stimulated FMF monocytes is NLRP3-dependent.

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Section: Resultssupporting

confidence: 84%

Section: Discussionsupporting

confidence: 64%

Increased NLRP3-dependent interleukin 1β secretion in patients with familial Mediterranean fever: correlation withMEFVgenotype

et al. 2013

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“…This study showed that the frequency of FMF-like symptoms increased from patients carrying a single low-penetrance mutation toward patients with two high-penetrance mutations with a decrease of periodic fever, aphthous stomatitis, pharyngitis, adenitis (PFAPA)-like symptoms [14].…”

Section: Introductionmentioning

confidence: 97%

The myths we believed in familial Mediterranean fever: what have we learned in the past years?

Özen

Batu

2015

Semin Immunopathol

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Familial Mediterranean fever is the most common monogenic periodic fever syndrome over the world especially in the eastern Mediterranean. It presents with recurrent and self-limited inflammatory attacks of fever and polyserositis along with high acute-phase reactants. The disease is associated with mutations in the MEFV gene that encodes pyrin, a component of inflammasome, which leads to exaggerated inflammatory response through uncontrolled production of interleukin 1. With the identification of the gene associated with the disease, we believed that everything was solved and that this was an ordinary monogenic disease with autosomal recessive inheritance. However, through the breathtaking progress in the basic research field as well as the clinical care of these patients, we have understood that the picture for this monogenic disorder was more complicated than we had anticipated. In this review, we have discussed the myths we believed in familial Mediterranean fever and how they have evolved during the past years.

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“…At first, it was believed that genetic testing would enable physicians to completely resolve the diagnostic difficulties associated with FMF and so to prevent its complications. However, over time, it has become clear that diagnostic interpretation can be very complex as some FMF patients may display no or only one of the known MEFV mutations,10 and conversely that the carriage of MEFV variants is not always accompanied by clinical symptoms.…”

Section: Introductionmentioning

confidence: 99%

Evidence-based recommendations for genetic diagnosis of familial Mediterranean fever

et al. 2015

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Familial Mediterranean fever (FMF) is a disease of early onset which can lead to significant morbidity. In 2012, Single Hub and Access point for pediatric Rheumatology in Europe (SHARE) was launched with the aim of optimising and disseminating diagnostic and management regimens for children and young adults with rheumatic diseases. The objective was to establish recommendations for FMF focusing on provision of diagnostic tools for inexperienced clinicians particularly regarding interpretation of MEFV mutations. Evidence-based recommendations were developed using the European League against Rheumatism standard operating procedure. An expert committee of paediatric rheumatologists defined search terms for the systematic literature review. Two independent experts scored articles for validity and level of evidence. Recommendations derived from the literature were evaluated by an online survey and statements with less than 80% agreement were reformulated. Subsequently, all recommendations were discussed at a consensus meeting using the nominal group technique and were accepted if more than 80% agreement was reached. The literature search yielded 3386 articles, of which 25 were considered relevant and scored for validity and level of evidence. In total, 17 articles were scored valid and used to formulate the recommendations. Eight recommendations were accepted with 100% agreement after the consensus meeting. Topics covered were clinical versus genetic diagnosis of FMF, genotype-phenotype correlation, genotype-age at onset correlation, silent carriers and risk of amyloid A (AA) amyloidosis, and role of the specialist in FMF diagnosis. The SHARE initiative provides recommendations for diagnosing FMF aimed at facilitating improved and uniform care throughout Europe

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Clinical impact ofMEFVmutations in children with periodic fever in a prevalent western European Caucasian population

Cited by 69 publications

References 27 publications

Increased NLRP3-dependent interleukin 1β secretion in patients with familial Mediterranean fever: correlation withMEFVgenotype

Increased NLRP3-dependent interleukin 1β secretion in patients with familial Mediterranean fever: correlation withMEFVgenotype

The myths we believed in familial Mediterranean fever: what have we learned in the past years?

Evidence-based recommendations for genetic diagnosis of familial Mediterranean fever

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