Familial Mediterranean fever mutation frequencies and carrier rates among a mixed Arabic population.

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, Amman, 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.