OBJECTIVE: Familial Mediterranean Fever (FMF) is an
autoinflammatory periodic disorder characterized by febrile and
painful attacks due to inflammation involving the serosal
membranes. The gene implicated in this disorder, MEFV, has been
cloned and mutations in its coding regions have been identified.
We aimed at identifying the frequency of MEFV mutations and
carrier frequency in a mixed Arabic population.
METHODS: We identified 29 probands from 29 unrelated
sibships segregating the disorder and representing the affected
individual cohort. We screened 200 anonymous deoxyribonucleic
acid (DNA) samples, representing a healthy adult cohort, for the
mutations found to be common in the affected individual cohort.
We also, screened anonymous DNA samples from 4 Arabic countries,
namely, Egypt (231), Syria (225), Iraq (176) and the Kingdom of
Saudi Arabia (107) thus enlarging our healthy adult cohort. The
study was carried out between 1999 and 2002 at Jordan University
of Science and Technology, Irbid and the University of Jordan,
RESULTS: Out of the 58 alleles of the 29 probands, only
31 mutations were identified and M694V and V726A are the most
common. The mutation E148Q was the most common among the healthy
adult cohort, but was not present in affected individuals. The
collective mutant allele frequency "q" was 0.101. The expected
carrier rate was 18.1% (one in 5.5) while the observed carrier
rate was 18.4% (one in 5.4).
CONCLUSION: E148Q has reduced penetrance and thus, a
proportion of the individuals genetically affected with FMF
remain asymptomatic. M694I and M680I are more prevalent in the
affected individuals cohort, which points to their higher
penetrance. The overall carrier rate is one in 5, but the
selective heterozygote advantage could not be demonstrated in
this study due to the relatively small sample size.
Department of Biochemistry, School of Medicine, Jordan
University of Science and Technology, Irbid, Jordan.