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Higher than expected carrier rates for familial Mediterranean fever in various Jewish ethnic groups
N Stoffman1, N Magal, T Shohat
1Department of Medical Genetics, FMRC, Schneider Children's Medical Center of Israel, and Rabin Medical Center, Petah Tikva, Israel.
Abstract:
Familial Mediterranean fever (FMF) is an autosomal recessive disease characterised by recurrent attacks of inflammation of serosal membranes. Amyloidosis leading to renal failure is the most severe complication in untreated patients. In Israel FMF is most frequent among Jews of North African origin. Recently the causative gene (MEFV) has been found and the common mutations characterised. The aim of this study was to investigate the carrier rates of the common MEFV mutations among 400 healthy members of four different ethnic groups (100 in each group) in Israel, and to compare the distribution of the different mutations between FMF carriers and patients. We found a high frequency of carriers among Jews from the various ethnic groups. In North African Jews it was 22%, in Iraqi Jews 39%, in Ashkenazi Jews 21%, and in Iranian Jews 6%. The distribution of the four most common MEFV mutations among healthy individuals (M694V 29%, V726A 16%, M6801 2% and E148Q 53%) was significantly different (P < 0.003) from that found in patients (M694V 84.4%, V726A 9.0%, M6801 0% and E148Q 6.6%). Six healthy asymptomatic individuals were found to carry mutations in both alleles: two homozygotes for E148Q and four compound heterozygotes E148Q/other. These results demonstrate a very high carrier rate among all Jewish ethnic groups. They confirm that mutation E148Q is associated with a milder phenotype, which explains the lower prevalence of FMF among the Ashkenazi and Iraqi Jews. This study raises the question of the need for molecular screening for M694V homozygotes in the Israeli North African Jewish community.
Insights
Familial Mediterranean fever (FMF) carrier rates are high across Israeli Jewish ethnic groups. The E148Q mutation is common and linked to milder FMF, while M694V homozygotes warrant screening in North African Jews.
Area of Science:
- Genetics
- Immunology
- Epidemiology
Background:
- Familial Mediterranean fever (FMF) is an autosomal recessive inflammatory disease.
- Amyloidosis and renal failure are severe complications of untreated FMF.
- FMF is prevalent in specific ethnic groups, notably North African Jews in Israel.
Purpose of the Study:
- To determine carrier rates of common MEFV gene mutations in healthy individuals from four Israeli ethnic groups.
- To compare the distribution of MEFV mutations between FMF carriers and patients.
- To investigate the association of specific MEFV mutations with FMF phenotype severity.
Main Methods:
- Genotyping of 400 healthy individuals from four Israeli ethnic groups (North African, Iraqi, Ashkenazi, Iranian Jews).
- Analysis of carrier frequencies for common MEFV mutations (M694V, V726A, M680I, E148Q).
- Comparison of mutation distribution in healthy carriers versus FMF patients.
Main Results:
- High carrier rates for MEFV mutations were observed across all studied Jewish ethnic groups.
- Carrier rates varied significantly: North African Jews (22%), Iraqi Jews (39%), Ashkenazi Jews (21%), Iranian Jews (6%).
- The distribution of MEFV mutations differed significantly between healthy carriers and FMF patients, with E148Q being more prevalent in carriers and M694V in patients.
Conclusions:
- A very high carrier rate for MEFV mutations exists in all Israeli Jewish ethnic groups.
- The E148Q mutation is associated with a milder FMF phenotype, explaining lower prevalence in certain groups.
- Molecular screening for M694V homozygotes is suggested for the North African Jewish community in Israel.