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

Familial Mediterranean fever (FMF) is an autosomal recessive disease charac terised by recurrent attacks of inflammation of serosal membranes. Amyloido sis is the most severe complication of the disease. The aim of this study w as to investigate the genotype-phenotype correlation and specifically the a ssociation between amyloidosis and the four common mutations in exon 10 of the gene causing FMF (MEFV) in a total of 83 FMF families from three ethnic groups: North African Jews, Armenians and Turks. A significant association was found between amyloidosis and the specific mutation at the MEFV gene: Met694Val (RR = 1.41, P = 0.02). Amyloidosis was present in 18 out of 87 ho mozygous FMF patients (20.7%) and in only two out of the 41 compound hetero zygous FMF patients (4.9%). No patients carrying other mutations had amyloi dosis. There was no significant association between the various mutations a nd the type or severity of the FMF symptoms. This finding underscores the i mportance of performing molecular studies on all suspect FMF patients. In a ddition to providing accurate diagnosis, these tests allow identification o f presymptomatic genetically affected individuals, detection of carriers an d assessment of the risk for amyloidosis in later life.