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Familial Mediterranean fever: prevalence, penetrance and genetic drift
R Gershoni-Baruch1, M Shinawi, K Leah
1Institute of Human Genetics, Rambam Medical Center, Haifa, Isreal. rgershoni@rambam.health.gov.il
Abstract:
FMF is widely distributed in populations inhabiting the Mediterranean basin. It is mainly attributed to five founder mutations (M680I, M694V, M694I, V726A, E148Q) in the MEFV gene. The frequencies and distribution of these mutations in 146 FMF patients, of Arab and Jewish descent, were compared to that observed in 1173 healthy individuals of pertinent ethnic groups. Five mutations accounted for 91% of FMF chromosomes in our patients. Mutation M694V, predominant in North African Jews, was observed in all patients other than Ashkenazi Jews; mutation V726A was prevalent among all patients other than North African Jews; mutations M694I and M680I were mainly confined to Arab patients. Overall carrier rates, for four mutations (M680I, M694V, V726A, E148Q), were extremely high in our healthy cohort composed of Ashkenazi (n=407); Moroccan (n=243); Iraqi Jews (n=205); and Muslim Arabs (n=318); calculated at 1 : 4.5; 1 : 4.7; 1 : 3.5 and 1 : 4.3 respectively. The V726A allele prevalent among Ashkenazi and Iraqi Jews and Muslim Arabs (carrier rates: 7.4, 12.8 and 7.3%, respectively) was not found among Moroccan Jews. The M694V allele detected among Moroccan and Iraqi Jews and Muslim Arabs (carrier rates 11.1, 2.9 and 0.6%, respectively) was not observed among Ashkenazim. The overall frequency of mutations V726A and E148Q in Ashkenazim, Iraqi Jews and Arabs indicates that the bulk of individuals that comply with the genetic definition of FMF remain asymptomatic.
Insights
Familial Mediterranean fever (FMF) mutations are common in Mediterranean populations. Specific MEFV gene mutations show distinct ethnic distributions, with high carrier rates in healthy individuals, many remaining asymptomatic.
Area of Science:
- Genetics
- Population Health
- Molecular Biology
Background:
- Familial Mediterranean fever (FMF) is a genetic autoinflammatory disorder prevalent in Mediterranean populations.
- The disease is primarily caused by mutations in the MEFV gene, with five founder mutations identified.
Purpose of the Study:
- To investigate the frequencies and ethnic distribution of five common MEFV gene mutations in FMF patients and healthy individuals.
- To compare mutation patterns between Arab and Jewish ethnic groups in the Mediterranean basin.
Main Methods:
- Genotyping of 146 FMF patients and 1173 healthy individuals from various Arab and Jewish ethnic backgrounds.
- Analysis of mutation frequencies for M680I, M694V, M694I, V726A, and E148Q in the MEFV gene.
Main Results:
- Five MEFV mutations accounted for 91% of FMF chromosomes in patients.
- Distinct mutation patterns were observed: M694V was predominant in North African Jews, V726A in non-North African Jews, and M694I/M680I in Arab patients.
- High carrier rates for FMF mutations were found in healthy individuals across Ashkenazi, Moroccan, Iraqi Jewish, and Muslim Arab cohorts.
Conclusions:
- The study highlights significant ethnic variations in MEFV mutation distribution among Mediterranean populations.
- High carrier frequencies in healthy populations suggest a substantial number of individuals may be asymptomatic carriers of FMF-associated mutations.
- Understanding these genetic patterns is crucial for genetic counseling and carrier screening programs.