Ms Marek-Yagel and Dr. Berkun contributed equally to this work.
Clinical disease among patients heterozygous for familial mediterranean fever†
Article first published online: 28 MAY 2009
Copyright © 2009 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 60, Issue 6, pages 1862–1866, June 2009
How to Cite
Marek-Yagel, D., Berkun, Y., Padeh, S., Abu, A., Reznik-Wolf, H., Livneh, A., Pras, M. and Pras, E. (2009), Clinical disease among patients heterozygous for familial mediterranean fever. Arthritis & Rheumatism, 60: 1862–1866. doi: 10.1002/art.24570
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.
- Issue published online: 28 MAY 2009
- Article first published online: 28 MAY 2009
- Manuscript Accepted: 9 MAR 2009
- Manuscript Received: 16 JUN 2008
To define the molecular basis of familial Mediterranean fever (FMF) in patients with only 1 mutation in the MEFV gene.
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.
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.
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.