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Orphanet Journal of Rare Diseases
Published in: Orphanet Journal of Rare Diseases 1/2015

Open Access 01-12-2015 | Research

Familial Mediterranean fever without MEFV mutations: a case–control study

Authors: Ilan Ben-Zvi, Corinne Herskovizh, Olga Kukuy, Yonatan Kassel, Chagai Grossman, Avi Livneh

Published in: Orphanet Journal of Rare Diseases | Issue 1/2015

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Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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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Metadata
Title
Familial Mediterranean fever without MEFV mutations: a case–control study
Authors
Ilan Ben-Zvi
Corinne Herskovizh
Olga Kukuy
Yonatan Kassel
Chagai Grossman
Avi Livneh
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Orphanet Journal of Rare Diseases / Issue 1/2015
Electronic ISSN: 1750-1172
DOI
https://doi.org/10.1186/s13023-015-0252-7

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