Prevalence and distribution of MEFV mutations among Arabs from the Maghreb patients suffering from familial Mediterranean fever

Abstract

Familial Mediterranean fever (FMF) is an autosomal recessive inherited disease caused by mutations in MEFV. This disease is characterized by recurrent episodes of fever accompanied with topical signs of inflammation. Some patients can develop renal amyloidosis. We prospectively investigated MEFV mutations in a cohort of 209 unrelated Arab patients from Maghreb (85 Algerians, 87 Moroccans, and 37 Tunisians) with a clinical suspicion of FMF. FMF is the main cause of periodic fever syndrome in Maghreb. The most frequent MEFV mutations in this cohort were M694V and M694I. These mutations account for different proportions of the MEFV mutations in Algeria (5%, 80%), Morocco (49%, 37%), and Tunisia (50%, 25%) patients. M694I mutation is specific to the Arab population from Maghreb. Other rare mutations were observed: M680L, M680I, A744S, V726A, and E148Q. We estimated the frequency of MEFV mutation carriers among the Arab Maghrebian population at around 1%, which is significantly lower than in non-Ashkenazi Jews, Armenians or Turks.

Familial Mediterranean Fever in the World

“…In addition to the above countries, FMF is found in significant numbers in North African countries, Greece, Crete, France, Germany, Italy, and the US (11)(12)(13)(14). In recent years, approximately 100 cases have been reported in Japan (15,16, and Tsuchiya-Suzuki A, et al: unpublished observations).…”

Founder Effect and Estimation of the Age of the c.892C>T (p.Arg298Cys) Mutation in LMNA Associated to Charcot‐Marie‐Tooth Subtype CMT2B1 in Families from North Western Africa

“…The relative homogeneity of populations from the Maghreb has often been underlined, and several founder mutations/effects have already been reported in North African (including Algerian) populations for various autosomal recessive hereditary diseases, such as: limb girdle muscular dystrophy type LGMD2C (Noguchi et al 1995), ataxia with isolated vitamin E deficiency (AVED) (Ouahchi et al 1995), Allgrove syndrome (Genin et al 2004), Unverricht-Lundborg disease (ULD) (Moulard et al 2002), Parkinson disease (Lesage et al 2005), Mal de Meleda disease (MdM) (Fischer et al 1998), Familial Mediterranean Fever (Belmahi et al 2006), or ß-thalassemias (Bennani et al 1994).…”

Population genetics of familial Mediterranean fever: a review

“…In other words, this mutation was present in North Africa before Arabization and Islamicization started in the 7th century CE. 21 Consequently, in this particular case, historical records are able to explain the presence of dissimilar patterns of the M694V and M694I mutations' distribution in the Arabs of North Africa. Available SNP haplotype data support the view that chromosomes with E148Q mutation from different ethnic groups probably share a common progenitor, thus implicating a founder effect.…”

“…During the second wave of migration, which continued more than two centuries, the Jewish population settled mainly in Morocco. 21 The M694I mutation also might be considered as ancient, as it is not a recurrent mutation and is present in the Berbers, the indigenous population of the Maghreb. In other words, this mutation was present in North Africa before Arabization and Islamicization started in the 7th century CE.…”