GENOTYPIC DIAGNOSIS OF FAMILIAL MEDITERRANEAN FEVER (FMF) USING NEW MICROSATELLITE MARKERS - EXAMPLE OF 2 EXTENSIVE NON-ASHKENAZI JEWISH PEDIGREES

Familial Mediterranean fever is an autosomal recessive disease charact erised by multiple attacks of serosal inflammation in the absence of t reatment. In the absence of timely diagnosis, renal amyloidosis is a l ife threatening complication. The diagnosis is often missed because no specific test is available. Early colchicine treatment prevents attac ks and renal complications. The FMF gene (MEF) has been mapped to chro mosome 16p13.3 but has not yet been identified. We compared the suitab ility of a series of microsatellite markers (four of them were new) an d propose the routine use of seven of these markers, exhibiting allele s in strong linkage disequilibrium with the disease and informative in 100% of diagnosed patients. Moreover, the discovery of a homozygous s tatus for the 3-3-9 (or 3-3-18) haplotype at the core loci (D16S3070, D16S3082, and D16S3275), which was found in 73% non-Ashkenazi Jewish p atients, points to a diagnosis of FMF, even in sporadic cases, with a risk of error of only 2.10(-5). Two extensive pedigrees covering most indications for genetic counselling are presented, showing that it is now possible both prospectively and retrospectively to identify member s likely to have MEF mutations. With the help of this accurate test, c olchicine treatment can be better targeted, especially where the sympt omatology is mild or atypical.