title: Common MEFV mutations among Jewish ethnic groups in Israel: high frequency of carrier and phenotype III states and absence of a perceptible biological advantage for the carrier state.
abstract: Familial Mediterranean fever (FMF) is an autosomal recessive disease, characterized by recurrent attacks of fever and inflammation of serosal membranes and gradual development of nephropathic amyloidosis. The recent cloning of the FMF gene (MEFV) and identification of disease-associated mutations in most patients made the direct determination of FMF carrier frequency feasible. The aim of the present study was to investigate the carrier rate of the most common MEFV mutations among different Jewish ethnic groups in Israel. Further, an attempt was made to elucidate the possible biological advantage that the heterozygote state may confer. Three hundred Ashkenazi, 101 Iraqi, and 120 Moroccan Jews were screened for the E148Q, V726A, and M694V mutations (at least two most common mutations per group), with a resulting overall carrier frequency in the respective ethnic group of 14%, 29%, and 21%. No difference in morbidity between Ashkenazi carriers and non-carriers of MEFV mutations was discerned, although an excess of febrile episodes in carriers of the V726A and in carriers of either V726A or E148Q was evident (P < 0.02 and P < 0.05, respectively). The frequency of subjects with two MEFV mutations but not expressing FMF (phenotype III) was 1:300 in Ashkenazi Jews and 1:25 in Iraqi Jews, exceeding the reported rate of overt FMF in these ethnic groups by 40-240 fold. These results affirm the high carrier rate among the studied Jewish ethnic groups in Israel and suggest that most subjects with FMF mutations are unaffected.
authors.affiliation: Heller Institute of Medical Research, Sheba Medical Center, Tel Hashomer, and Sackler Faculty of Medicine Tel Aviv University, Tel Aviv, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Kogan
authors.forename: Y
authors.initials: Y
authors.lastname: Shinar
authors.forename: M
authors.initials: M
authors.lastname: Lidar
authors.forename: A
authors.initials: A
authors.lastname: Revivo
authors.forename: P
authors.initials: P
authors.lastname: Langevitz
authors.forename: S
authors.initials: S
authors.lastname: Padeh
authors.forename: M
authors.initials: M
authors.lastname: Pras
authors.forename: A
authors.initials: A
authors.lastname: Livneh
mesh_terms: D000483:Alleles; D003598:Cytoskeletal Proteins; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D010505:Familial Mediterranean Fever / Q000235:genetics; D005787:Gene Frequency; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D007493:Iraq / Q000208:ethnology; D007557:Israel; D007585:Jews / Q000235:genetics*; D009018:Morocco / Q000208:ethnology; D009154:Mutation; D020125:Mutation, Missense; D010641:Phenotype; D011506:Proteins / Q000235:genetics*; D000071198:Pyrin
chemical_list: D003598:Cytoskeletal Proteins; C000604192:MEFV protein, human; D011506:Proteins; D000071198:Pyrin; D004247:DNA