MEFV mutations in Moroccan patients suffering from familial Mediterranean Fever

Abstract

Familial Mediterranean Fever (FMF, MIM 249100) is an autosomal recessive disease mainly affecting patients of the Mediterranean basin. It is an autoinflammatory periodic disorder characterised by recurrent episodes of fever and abdominal pain, synovitis and pleuritis. FMF is caused by mutations in the Mediterranean Fever (MEFV) gene located on chromosome 16p13.3. Several mutations in the MEFV gene have been characterised in different populations. However, very little is known about mutations in the MEFV gene in patients with Moroccan origin. The aim of this study is to determine the clinical components of FMF and characterise mutations in the MEFV gene in Moroccan patients. The study was carried out on 120 unrelated Moroccan patients referred to the department of medical genetics in Rabat for suspicious FMF over a period of 10 years. Patients were screened for the most common MEFV mutations by direct sequencing of exons 2 and 10. Of the 120 unrelated patients investigated, 56 patients (47%) were carriers of one or two MEFV mutations, and 64 patients (53%) had no detected mutations. Of those with mutations, 24 were homozygous (44%), 13 were compound heterozygotes (24%), and 19 patients had only 1 identifiable mutation (32%). The most frequent mutation in Moroccan patients is M694V (47%), followed by M694I (32%), A744S (6.5%), M680L (4%), M694del (2%) and E148Q (6.5%). The R761H, K695R and I692del mutations were rarely encountered (less than 1%). The V726A mutation was not found in our study. Our data represent the first report of MEFV gene mutations causing FMF in Moroccans patients. The M694V and M694I mutations are the most common mutations found in MEFV gene in Moroccan population; while the most common mutation in Arabs from the Middle-East region, the V726A, was not found in our population.

Frequency of MEFV gene mutations in Hatay province, Mediterranean region of Turkey and report of a novel missense mutation (I247V)

“…Study Group, 2005;Yalcinkaya et al, 2000;Akin et al, 2010;Ceylan et al, 2012;Dogan et al, 2012;Etem, 2010;Pasa et al, 2008;Yilmaz et al, 2001). It is the most frequently seen mutation in populations where FMF is prevalent including Iranian Azerbaijani Turks (Bonyadi et al, 2009), Jews (Ben-Chetrit et al, 2000Dode et al, 2000), Arabs (Al-Alami et al, 2003;Ayesh et al, 2005;Belmahi et al, 2012;Gershoni-Baruch et al, 2001;Majeed et al, 2005;Mattit et al, 2006;Medlej-Hashim et al, 2000 and Armenians (Cazeneuve et al, 1999;Sarkisian et al, 2005). On the contrary to above-mentioned studies from Turkey and other countries, M694V was the third most commonly seen mutation in the present study with a frequency of 7.95%.…”

Common MEFV Mutations in Palestinian Patients with Familial Mediterranean Fever

“…Additionally, mutation p.M694V was the most frequent mutation and represented about 32% of the mutant alleles (Table 1). This mutation is also the most frequently seen mutation in FMF patients belonging to the four major Mediterranean (Armenians, Jews, Arabs and Turks) populations (e.g., Aksentijevich et al, 1999;Solak et al, 2008;Belmahi et al, 2012). These observations indicate that common MEFV mutations are actually old and had descended from ancestors (founders) common to the four populations.…”

Renal amyloidosis due to familial Mediterranean fever misdiagnosed

“…We assume that she might have an earlier nonMaghrebian ancestor. The data reported by our preliminary study,[12] and by the two cases, are prone to bring Moroccan clinicians’ attention to the relative frequency of this disease in Morocco. We encourage them to consider this pathology in their daily practice and to work in concert with geneticians and epidemiologists to run wider studies to characterize the clinical and molecular profile of FMF in our country and contribute to take better care of our patients.…”

“…As such, we have recently reported data on MEFV gene mutations causing FMF among Moroccans patients. [12] The most frequent mutation in Moroccan patients is M694V (47 %), followed by M694I (32 %), A744S (6.5 %), M680L (4 %), M694del (2%), and E148Q (6.5 %). There are no pathognomonic clinical symptoms of FMF and any specific biochemical abnormality.…”

“…[10] The V726A mutation is the second most frequent mutation in Arabs from Middle East, in Armenians and Turks,[16] while it was nonexistent in our population. [12] The patient's ancestors are Moroccan going back three generations. We assume that she might have an earlier nonMaghrebian ancestor.…”