title: Global epidemiology of Familial Mediterranean fever mutations using population exome sequences.
abstract: Familial Mediterranean fever (FMF) is an inherited disorder characterized by recurrent episodes of fever accompanied by sterile peritonitis, arthritis, and pleuritis. Many mutations in the MEFV gene have been identified as causing FMF. However, accompanying epidemiological information remains quite scarce except in some Mediterranean countries, and the degree of penetrance has been a subject of controversy. Here, I established a genetic epidemiology of full FMF mutations using two population exome studies. Of 57 mutations associated with FMF, 22 were detected in a total of 9007 individuals from two exome sequences. Exome-based epidemiology revealed the carrier rates of FMF in 28 populations in 19 countries by individual mutation and showed strong population specificity for the MEFV mutations. Unexpectedly high carrier rates suggested that some mutations are benign variants with no pathological significance and highlighted the need for caution in analyzing MEFV mutations. Similar approach could be used to uncover the incomplete or no penetrance of mutations in most inherited disorders.
authors.affiliation: Kobe University School of Medicine 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Fujikura
keywords: Allele frequency; Familial Mediterranean fever; epidemiology; exome; genetic diagnosis