Phenotype-genotype correlation in Jewish patients suffering from familial Mediterranean fever (FMF)

Abstract

Familial Mediterranean Fever is one of the most frequent recessive disease in non-Ashkenazi Jews. The gene responsible for the disease (MEFV) has very recently been identified. The M694V ('MED') mutation was found in about 80% of the FMF Jewish (Iraqi and North African) chromosomes. To see if the presence of this mutation could be correlated with particular traits of the disease, we examined a number of clinical features in a panel of 109 Jewish FMF patients with 0, 1 or 2 MED mutations. We showed that homozygosity for this mutation was significantly associated with a more severe form of the disease. In homozygous patients, the disease started earlier (mean age 6.4 + /-5 vs 13.6 + /-8.9) and both arthritis and pleuritis were twice as frequent as in patients with one or no M694V mutation. Moreover, 3/3 patients with amyloidosis displayed two MED mutations. No association was found with fever, peritonitis, response to colchicine and erysipeloid eruption. The present result strongly suggests the potential prognostic value of the presence of this mutation.

Phenotype–genotype correlation in familial Mediterranean fever: evidence for an association between Met694Val and amyloidosis

“…In our study population there were no significant differences in the clinical presentation of FMF patients carrying different mutations, although both Pras et al 20 and Dewalle et al 17 found that homozygosity for the Met694Val mutation was significantly associated with a more severe form of the disease. A possible explanation could be that the NAJ patients have a phenotype which is different from that of other ethnic groups, even when they have the same genotype.…”

“…Yalçinkaya et al 18 reported two patients with amyloidosis who were both compound heterozygotes Val726Ala/Met680Ile, and Dewalle et al 17 reported an Arab kindred where all the affected individuals were homozygotes for Met694Ile. The third case, reported by Pras,19 was one patient with systemic amyloidosis who was homozygous for Val726Ala.…”

“…[17][18][19] The aim of our study was to characterise the mutations in the MEFV gene in different ethnic groups, and to examine whether there is a correlation between the different mutations and the clinical symptoms in affected individuals. Specifically, we examined whether there is an association between FMF genotype and amyloidosis.…”

Familial Mediterranean Fever in the World

“…Following the isolation of the MEFV gene and mutations, numerous studies tested the genotype-phenotype correlations in FMF patients in different countries. When FMF was first discovered, it was shown that homozygosity for p.M694V was associated with more severe disease, including early onset, more frequent attacks, significantly more joint disease, a higher dose of colchicine needed to control attacks, and a higher rate of amyloidosis among patients not adequately treated (28). These results were confirmed in further studies performed in Israel, France (with Armenian patients), and in Middle Eastern countries (Jordan and Lebanon) (22)(23)(24).…”

Enhanced cytokine mRNA levels in attack-free patients with familial Mediterranean fever

“…We thus investigated the impact of the most common FMFassociated genotype, M694V/M694V, which is known to be correlated with a severe disease course. [21][22][23] We observed no significant difference in cytokine mRNA levels between M694V/M694V patients and other FMF patients with a different genotype (Figure 2b).…”