Abstract
BackgroundAlthough 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.MethodsMEFV 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.ResultsForty-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.ConclusionsMEFV 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.
Highlights
Familial Mediterranean fever (FMF) was originally defined as an autosomal recessive disorder, approximately 10–20% of familial Mediterranean fever (FMF) patients do not carry any FMF gene (MEFV) mutations
FMF was originally defined as an autosomal recessive disorder, approximately 25% of the patients carry only 1 MEditerranean FeVer gene (MEFV) mutation [5], and 10–20% carry no mutations at all [6]
Consecutive patients were enrolled successively, according to the order of arrival and divided into 3 groups, as follows: Study group: The study group consisted of MEFV mutation-negative FMF patients, identified as such according to their files
Summary
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. Familial Mediterranean fever (FMF) is an autosomal, recessively inherited autoinflammatory disease, associated with the MEditerranean FeVer gene (MEFV) and characterized by recurrent episodes of fever and serositis, mostly peritonitis, and pleuritis, pericarditis and synovitis [1,2]. A small number of these variants are unambiguously pathogenic and FMF was originally defined as an autosomal recessive disorder, approximately 25% of the patients carry only 1 MEFV mutation [5], and 10–20% carry no mutations at all [6]. Molecular analysis performed in previous studies confirmed the lack of other rare mutations in these patients [7,8]. If yielding, may help at most in atypical presentations [10]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
