Familial Mediterranean fever: High gene frequency among the non‐Ashkenazic and ashkenazic Jewish populations in Israel

Abstract

Familial Mediterranean fever (FMF) is an autosomal recessive recurrent episodic inflammatory disorder that occurs with high frequency in certain populations in the Mediterranean area. Using extended pedigree data of 90 FMF probands, we calculated the FMF gene frequency in various ethnic groups in Israel by analyzing the frequency in a total of 2,312 first cousins. The heterozygote frequencies were as follows: 1:4.9 (0.2 +/- 0.06) for the Libyan subgroup, 1:6.4 (0.16 +/- 0.03) for the other North African countries subgroup, 1:13.3 (0.07 +/- 0.04) for the Iraqi subgroup, 1:11.4 (0.09 +/- 0.06) for the Ashkenazic subgroup, and 1:29.4 (0.03 +/- 0.03) for the remaining ethnic groups. The observed number of affected parents and offspring of the probands was in agreement with the estimated gene frequency. Thus, the FMF gene frequency is very high in all Jewish ethnic groups in Israel, especially those originating in North African countries. This also explains the parent-to-off-spring transmission of FMF reported in North-African Jews.

Familial Mediterranean fever: prevalence, penetrance and genetic drift

“…Estimated carrier rates vary from 1/6 ± 1/7 in North African Jews, 1/13 in Iraqi Jews to 1/135 in Ashkenazi Jews. 3,4,11 It has been repeatedly shown, that the variable disease phenotype, severe in North African Jews, milder in Iraqi Jews and Druzes is at least partly due to allelic heterogeneity with mutation M694V being associated with a severe phenotype and amyloidosis, and mutation V726A with a milder form of the disease. 12 ± 14 The five common founder mutations are differentially distributed among our patients: M694V, predominant among North African Jews, was detected in all patients other than Ashkenazi Jews; V726A was observed in all patients other European Journal of Human Genetics FMF: Prevalence, penetrance and genetic drift R Gershoni-Baruch et althan North African Jews; M680I is common and confined to Arab patients; M694I is rare and confined to Arab patients; E148Q is occasionally encountered in patients from all ethnic groups.…”

“…1,2 It is very common in the populations at risk with estimated carrier rates of 1/6 in Armenians, 1/7 in North African Jews and 1/13 in Iraqi Jews. 3,4 The gene causing FMF (MEFV) has been cloned and five common founder mutations (M694V, V726A, M680I, M694I, E148Q), each segregating with one ancestral haplotype, were identified. 5 ± 8 SNP haplotype data, recently presented, is consistent with the opinion that each of these mutations share a common progenitor.…”

Higher than expected carrier rates for familial Mediterranean fever in various Jewish ethnic groups

“…This rate exceeds that expected by the prevalence of the disease, especially in Ashkenazi and Iraqi Jews, and therefore suggests that many patients in these ethnic groups are undiagnosed. Indeed, the carrier rate was previously estimated, based on family studies, to be as high as 1:5-1:7 among some nonAshkenazi Jewish populations, 16 and 1:7 among Armenians in California. 17 Owing to the high prevalence in Jews, Israeli doctors find themselves including FMF in their differential diagnosis quite often, especially when the patient is of North African origin.…”

Familial Mediterranean Fever in the World

“…Since the prevalence of FMF is approximately 1:400 to 1:1,000 (highest in the areas of Anatolia) and the population is approximately 70 million, it is estimated that Turkey has more than 100,000 patients with FMF (4 -6). In Israel, the prevalence is slightly more than 1:1,000 (depending on the ethnic group), and since the population is approximately 7 million, it is estimated that there are approximately 10,000 patients (7). Armenia is probably the next country with widespread FMF.…”