Familial Mediterranean fever in Lebanon: mutation spectrum, evidence for cases in Maronites, Greek orthodoxes, Greek catholics, Syriacs and Chiites and for an association between amyloidosis and M694V and M694I mutations

• Published in: European journal of human genetics : EJHG Vol. 9; no. 1; pp. 51 - 55
• Main Authors: Mansour, I, Delague, V, Cazeneuve, C, Dodé, C, Chouery, E, Pêcheux, C, Medlej-Hashim, M, Salem, N, El Zein, L, Levan-Petit, I, Lefranc, G, Goossens, M, Delpech, M, Amselem, S, Loiselet, J, Grateau, G, Mégarbane, A, Naman, R
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.01.2001
• Subjects: Alleles; Amyloidosis; Amyloidosis - genetics; Amyloidosis - pathology; Arthritis; Cytoskeletal Proteins; Disease; DNA - chemistry; DNA - genetics; DNA Mutational Analysis; Familial Mediterranean fever; Familial Mediterranean Fever - genetics; Familial Mediterranean Fever - pathology; Fever; Gene Frequency; Genetics; Genotype; Genotypes; Humans; Jewish people; Lebanon; Mutation; Phenotypes; Proteins - genetics; Pyrin; Pyrin protein; Religion; Religious orthodoxy; Severity of Illness Index; Lebanon; Beirut Lebanon
• DOI: 10.1038/sj.ejhg.5200574
• ISSN: 1018-4813

Seventy-nine unrelated Lebanese patients were tested for 15 mutations in the MEFV gene: A761H, A744S, V726A, K695R, M694V, M694I, M694del, M6801 (G --> C), M680I (G --> A) in exon 10, F479L in exon 5, P369S in exon 3, T267I, E167D and E148Q in exon 2, using PCR digestion, ARMS, DGGE and/or sequencing. Mutations were detected in patients belonging to all communities, most interestingly the Maronite, Greek orthodox, Greek catholic, Syriac and Chiite communities. The most frequent mutations are M694V and V726A (27% and 20% of the total alleles respectively). M694I, E148Q and M680I mutations account respectively for 9%, 8% and 5%. Each of the K695R, E167D and F479L mutations was observed once and all the remaining mutations were not encountered. Of the alleles 33% do not carry any of the studied mutations. The mutation spectra, clinical features and severity of the disease differed among the Lebanese communities. The genotype-phenotype analysis showed a significant association (P < 0.001) between amyloidosis and the presence of mutations at codon 694 in exon 10 (both M694V and M694I). None of the patients carrying other mutations developed amyloidosis.