MEFV mutations in Moroccan patients suffering from familial Mediterranean Fever.
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.
Department of Medical Genetics, National Institute of Health, 27, Avenue Ibn Battouta, BP 769, Rabat, Morocco.
Latifa
L
Belmahi
Imane Jaouad
IJ
Cherkaoui
Iman
I
Hama
Abdelaziz
A
Sefiani
D000293:Adolescent; D000328:Adult; D018912:Arabs / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D003598:Cytoskeletal Proteins / Q000235:genetics*; D010505:Familial Mediterranean Fever / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009018:Morocco; D009154:Mutation; D000071198:Pyrin
D003598:Cytoskeletal Proteins; C000604192:MEFV protein, human; D000071198:Pyrin
Nucleic Acids Res. 1988 Feb 11;16(3):1215
3344216
Semin Arthritis Rheum. 2007 Jun;36(6):397-401
17276496
Rheumatol Int. 2006 Apr;26(6):489-96
16283319
Semin Arthritis Rheum. 2002 Jun;31(6):371-6
12077709
Saudi Med J. 2003 Oct;24(10):1055-9
14578967
Eur J Med Genet. 2006 Nov-Dec;49(6):481-6
16627024
Lancet. 2006 Mar 25;367(9515):1016-24
16564365
Semin Arthritis Rheum. 2005 Jun;34(6):813-8
15942916
Arthritis Rheum. 2009 Jun;60(6):1862-6
19479871
Hum Mol Genet. 1998 Aug;7(8):1317-25
9668175
Ann Intern Med. 1998 Oct 1;129(7):539-42
9758573
Hum Mutat. 2003 Feb;21(2):146-50
12552562
J Biosoc Sci. 2009 Sep;41(5):575-81
19433002
Cell. 1997 Aug 22;90(4):797-807
9288758
Eur J Hum Genet. 2000 May;8(5):360-6
10854096
Am J Med Genet. 2000 Jun 5;92(4):241-6
10842288
C R Biol. 2006 Feb;329(2):71-4
16439335