Clinical disease among patients heterozygous for familial mediterranean fever

Authors

  • Dina Marek-Yagel,

    1. Danek Gertner Institute of Human Genetics, Sheba Medical Center, Tel Hashomer, Israel, and Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Israel
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    • Ms Marek-Yagel and Dr. Berkun contributed equally to this work.

  • Yackov Berkun,

    1. Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Israel, and Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Israel
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    • Ms Marek-Yagel and Dr. Berkun contributed equally to this work.

  • Shai Padeh,

    1. Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Israel, and Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Israel
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  • Almogit Abu,

    1. Danek Gertner Institute of Human Genetics, Sheba Medical Center, Tel Hashomer, Israel, and Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Israel
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  • Haike Reznik-Wolf,

    1. Danek Gertner Institute of Human Genetics, Sheba Medical Center, Tel Hashomer, Israel, and Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Israel
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  • Avi Livneh,

    1. Heller Institute of Medical Sciences, Sheba Medical Center, Tel Hashomer, Israel, and Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Israel
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  • Mordechai Pras,

    1. Heller Institute of Medical Sciences, Sheba Medical Center, Tel Hashomer, Israel, and Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Israel
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  • Elon Pras

    Corresponding author
    1. Danek Gertner Institute of Human Genetics, Sheba Medical Center, Tel Hashomer, Israel, and Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Israel
    • Institute of Human Genetics, Sheba Medical Center, Tel Hashomer 52621, Israel
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  • Presented by Ms Marek-Yagel in partial fulfillment of the requirements for a PhD degree, Tel Aviv University, Sackler School of Medicine, Tel Aviv, Israel.

Abstract

Objective

To define the molecular basis of familial Mediterranean fever (FMF) in patients with only 1 mutation in the MEFV gene.

Methods

Genetic analysis was performed in 20 FMF patients, including full sequencing of complementary DNA (cDNA) samples and multiplex ligation-dependent probe amplification analysis. In patients with first-degree relatives with FMF, haplotype analysis was also performed.

Results

A second mutation was found in 2 patients. In the other 18 patients, we could not identify additional mutations, large genomic deletions, or duplications. Analysis of single-nucleotide polymorphisms along the cDNA ruled out a lack of expression of 1 of the alleles. In 2 of the 3 families in which more than 1 sibling had FMF, we showed that the affected siblings inherited a different MEFV allele from the parent who did not have the MEFV mutation.

Conclusion

These findings are highly consistent with the existence of a clinical phenotype among some patients who are heterozygous for FMF and could explain the vertical transmission in some families. A single mutation in the MEFV gene may be much more common than was previously thought and may include up to 25% of patients who are diagnosed as having FMF.

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