MEFV gene mutations in familial Mediterranean fever phenotype II patients with renal amyloidosis in childhood: a retrospective clinicopathological and molecular study

Background. Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by recurring attacks of fever and serositis. The definition of the mutated gene has allowed molecular diagnosis of the disease. The most important complication of FMF is the development of AA type secondary amyloidosis. In a group of patients clinically designated as phenotype II amyloidosis patients, renal amyloidosis develops without being preceded by typical attacks of the disease. In this study, the mutations of the MEFV gene were analysed in a group of patients clinically recognized as phenotype II. Methods. DNA samples were obtained from tissue samples of the subjects. PCR–RFLP methods were used to analyse the M694V, M680I, V726A and E148Q mutations that have been previously defined by us to be the most common mutations in our Turkish cohort. Results. The distribution of the four most common mutations among phenotype II patients was 38% for M694V, 8% for M680I, 4% for V726A and 4% for E148Q. Conclusions. In phenotype II amyloidosis patients, the distribution of the four common MEFV mutations was not significantly different from that found in all FMF patients with typical symptoms who do or do not develop amyloidosis. We therefore suggest that secondary genetic or environmental factors are operative in the development of secondary amyloidosis in patients with FMF.