The E148Q MEFV allele is not implicated in the development of familial Mediterranean fever

Authors

  • Dimitri Tchernitchko,

    1. Service de Biochimie, hôpital Henri-Mondor, Créteil, INSERM U.468 Génétique moléculaire et physiopathologie, Créteil, France
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    • These authors contributed equally to this work

  • Marie Legendre,

    1. Service de Biochimie, hôpital Henri-Mondor, Créteil, INSERM U.468 Génétique moléculaire et physiopathologie, Créteil, France
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    • These authors contributed equally to this work

  • Cécile Cazeneuve,

    1. INSERM U.468 Génétique moléculaire et physiopathologie, Créteil, France
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  • Andrée Delahaye,

    1. Service de Biochimie, hôpital Henri-Mondor, Créteil, INSERM U.468 Génétique moléculaire et physiopathologie, Créteil, France
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  • Florence Niel,

    1. Service de Biochimie, hôpital Henri-Mondor, Créteil, INSERM U.468 Génétique moléculaire et physiopathologie, Créteil, France
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  • Serge Amselem

    Corresponding author
    1. Service de Biochimie, hôpital Henri-Mondor, Créteil, INSERM U.468 Génétique moléculaire et physiopathologie, Créteil, France
    2. INSERM U.468 Génétique moléculaire et physiopathologie, Créteil, France
    • Service de Biochimie – INSERM U.468, Hôpital Henri-Mondor, 51 avenue du Maréchal de-Lattre-de-Tassigny, 94010 Créteil, France
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Abstract

Familial Mediterranean fever (FMF) is an autosomal recessive disorder characterized by recurrent attacks of fever and serositis, common in populations of Armenian, Arab, Sephardic Jewish and Turkish origin. Early diagnosis is crucial to start colchicine therapy that prevents the occurrence of attacks and renal amyloidosis. In the absence of functional test for FMF, the diagnosis remains clinical and is generally confirmed by molecular analysis of the MEFV gene. More than 40 missense mutations and two in-frame deletions have been reported, most of them being located in exon 10 of the gene. The M694V (c.2080A>G) mutation, the most frequent defect, is responsible for a severe phenotype when present in the homozygous state. The E148Q (c.442G>C) sequence variant, which is situated in exon 2, is also common, but its role in FMF is controversial. In order to assess the implication of the E148Q variation in FMF, we investigated 233 patients of Sephardic Jewish origin living in France and 213 disease-free relatives of these patients. The frequency of the E148Q allele was found to be similar in the two groups (3.62% and 3.75%, respectively, p=0.93). Most importantly, the frequency of the M694V/E148Q compound heterozygous genotype was comparable between the patients group (3.9%) and the healthy relatives group (4.2%, p=0.85). This population-based study, therefore, strongly supports the hypothesis that E148Q is a just a benign polymorphism and not a disease-causing mutation. Considering this variant as a mutation may lead to set false positive diagnoses and to neglect the likely existence of genetic heterogeneity in FMF © 2003 Wiley-Liss, Inc.

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