• Dina Marek-Yagel, Yackov Berkun, Shai Padeh, Almogit Abu, Haike Reznik-Wolf, Avi Livneh, Mordechai Pras, and Elon Pras.
• Danek Gertner Institute of Human Genetics, Sheba Medical Center, Tel Hashomer, Israel, and Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Israel.
• Arthritis Rheum. 2009 Jun 1; 60 (6): 1862-6.

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