Clinical disease among patients heterozygous for familial Mediterranean fever.
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.


CONCLUSIONS
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.
Marek-Yagel
Dina
D
Danek Gertner Institute of Human Genetics, Sheba Medical Center, Tel Hashomer, Israel, and Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Israel.
Berkun
Yackov
Y
Padeh
Shai
S
Abu
Almogit
A
Reznik-Wolf
Haike
H
Livneh
Avi
A
Pras
Mordechai
M
Pras
Elon
E
D000293:Adolescent; D000328:Adult; D000483:Alleles; D002648:Child; D002675:Child, Preschool; D003598:Cytoskeletal Proteins / Q000235:genetics*; D004247:DNA / Q000235:genetics; D010505:Familial Mediterranean Fever / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D005820:Genetic Testing; D006239:Haplotypes / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D000071198:Pyrin; D055815:Young Adult
D003598:Cytoskeletal Proteins; C000604192:MEFV protein, human; D000071198:Pyrin; D004247:DNA