Genotype-phenotype Correlation in a Large Group of Turkish Patients with Familial Mediterranean Fever: Evidence for Mutation-independent Amyloidosis

Objectives: Differences in clinical manifestations of familial Mediterranean fever (FMF) between different ethnic groups have been documented. The FMF gene was recently cloned and four missense mutations (Met694Val, Met680Ile, Val726Ala, and Met694Ile) that account for a large percentage of the patients were identified. The results of initial mutation studies have led to the hypothesis that phenotypic variation of the disease may be attributable to the existence of some of these mutations. The purpose of this study was to evaluate whether this phenotypic variation is associated with the existence of particular mutations in Turkish FMF patients living in Turkey.

Methods: Four missense mutations and genotype-phenotype correlation were investigated in 167 Turkish FMF patients. The patients were grouped according to the presence of the Met694Val and the Met680Ile mutations, and 12 clinical parameters were compared between the groups.

Results: The presence of the Met694Val mutation was not found to be associated with a severe form of the disease or the development of amyloidosis. Arthritis frequency was found to be lower in the patients with homozygous Met680Ile mutation.

Conclusions: None of the four missense mutations is associated with a severe disease or the development of amyloidosis in Turkish FMF patients living in Turkey. The influence of unknown environmental factors and/or the presence of other genetic changes are necessary to explain the phenotypic variation of the disease and the development of amyloidosis.