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.
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.
Mansour
I
I
Unité de Génétique Médicale, Université Saint Joseph, Faculté de Médecine, Beirut, Lebanon. CTSHD@cyberia.net.lb
Delague
V
V
Cazeneuve
C
C
Dodé
C
C
Chouery
E
E
Pêcheux
C
C
Medlej-Hashim
M
M
Salem
N
N
El Zein
L
L
Levan-Petit
I
I
Lefranc
G
G
Goossens
M
M
Delpech
M
M
Amselem
S
S
Loiselet
J
J
Grateau
G
G
Mégarbane
A
A
Naman
R
R
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
D003598:Cytoskeletal Proteins; C000604192:MEFV protein, human; D011506:Proteins; D000071198:Pyrin; D004247:DNA