title: 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.
abstract: 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.
authors.affiliation: Unité de Génétique Médicale, Université Saint Joseph, Faculté de Médecine, Beirut, Lebanon. CTSHD@cyberia.net.lb
authors.forename: I
authors.initials: I
authors.lastname: Mansour
authors.forename: V
authors.initials: V
authors.lastname: Delague
authors.forename: C
authors.initials: C
authors.lastname: Cazeneuve
authors.forename: C
authors.initials: C
authors.lastname: Dodé
authors.forename: E
authors.initials: E
authors.lastname: Chouery
authors.forename: C
authors.initials: C
authors.lastname: Pêcheux
authors.forename: M
authors.initials: M
authors.lastname: Medlej-Hashim
authors.forename: N
authors.initials: N
authors.lastname: Salem
authors.forename: L
authors.initials: L
authors.lastname: El Zein
authors.forename: I
authors.initials: I
authors.lastname: Levan-Petit
authors.forename: G
authors.initials: G
authors.lastname: Lefranc
authors.forename: M
authors.initials: M
authors.lastname: Goossens
authors.forename: M
authors.initials: M
authors.lastname: Delpech
authors.forename: S
authors.initials: S
authors.lastname: Amselem
authors.forename: J
authors.initials: J
authors.lastname: Loiselet
authors.forename: G
authors.initials: G
authors.lastname: Grateau
authors.forename: A
authors.initials: A
authors.lastname: Mégarbane
authors.forename: R
authors.initials: R
authors.lastname: Naman
mesh_terms: D000686:Amyloidosis / Q000235:genetics / Q000473:pathology; D003598:Cytoskeletal Proteins; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D010505:Familial Mediterranean Fever / Q000235:genetics* / Q000473:pathology; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007861:Lebanon; D009154:Mutation; D011506:Proteins / Q000235:genetics*; D000071198:Pyrin; D012067:Religion; D012720:Severity of Illness Index
chemical_list: D003598:Cytoskeletal Proteins; C000604192:MEFV protein, human; D011506:Proteins; D000071198:Pyrin; D004247:DNA