Autoinflammatory diseases are a group of disorders characterized by seemingly unprovoked inflammation in the absence of high-titer autoantibodies or antigen-specific T cells. Familial Mediterranean Fever (FMF) is an autosomal recessive disorder. It is characterized by recurrent self-limiting episodes of fever and painful polyserositis. FMF is prevalent in specific ethnic groups—namely, non-Ashkenazi Jews, Armenians, Turks, and Arabs. There seems to be a distinctive clinical picture in Arab patients with FMF, and the range and distribution of MEFV mutations is different from that noted in other commonly affected ethnic groups.

The aim of this study is to delineate the spectrum and distribution of MEFV mutations amongst an Arabic FMF patient cohort and to assist the genotype-phenotype correlation in these patients.

We have collected DNA samples from 188 FMF patients (from Qatar, Jordan and Palestine) who have been clinically diagnosed with FMF, according to international and validated diagnostic criteria. We have designed primers to cover the entire genomic region of MEFV. As a first tier, mutation detection is done by resequencing the entire coding sequence and splice sites; as a second tier the rest of the genomic region including the promoter are resequenced.

In the first tier, we have identified 191 out of 376 mutant alleles (50%) by resequencing the entire coding region and splice sites of MEFV. In addition, resequencing of the entire genomic region of 100 patients who had only one identifiable allele was carried resulting in the identification of specific haplotypes and we are currently investigating the phenotypic significance of these haplotypes.

The spectrum of MEFV mutations in Arabs seems different from other ethnic groups commonly affected by FMF. The fraction of the identifiable disease causing alleles is the lowest amongst the commonly affected ethnic groups. The results of the genomic resequencing of MEFV may provide some insight into the role of non-coding sequences and may explain the molecular pathology of FMF. Thereby, we are currently working on the development of a low cost and high throughput technique to facilitate the resequencing of the entire genomic sequence of MEFV using Next Generation sequencing technology.


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