{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T04:35:59Z","timestamp":1792643759595,"version":"4.5.0"},"reference-count":41,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2009,5,28]],"date-time":"2009-05-28T00:00:00Z","timestamp":1243468800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2009,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Familial Mediterranean fever (FMF) has traditionally been considered an autosomal\u2010recessive disease; however, it has been observed that a substantial number of patients with clinical FMF possess only 1 demonstrable <jats:italic>MEFV<\/jats:italic> mutation. The purpose of this study was to perform an extensive search for a second <jats:italic>MEFV<\/jats:italic> mutation in 46 patients diagnosed clinically as having FMF and carrying only 1 high\u2010penetrance FMF mutation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p><jats:italic>MEFV<\/jats:italic> and other candidate genes were sequenced by standard capillary electrophoresis. In 10 patients, the entire 15\u2010kb <jats:italic>MEFV<\/jats:italic> genomic region was resequenced using hybridization\u2010based chip technology. <jats:italic>MEFV<\/jats:italic> gene expression levels were determined by quantitative reverse transcription\u2013polymerase chain reaction. Pyrin protein levels were examined by Western blotting.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A second <jats:italic>MEFV<\/jats:italic> mutation was not identified in any of the patients who were screened. Haplotype analysis did not identify a common haplotype that might be associated with the transmission of a second FMF allele. Western blots did not demonstrate a significant difference in pyrin levels between patients with a single mutation and those with a double mutation; however, FMF patients of both types showed higher protein expression as compared with controls and with non\u2010FMF patients with active inflammation. Screening of genes encoding pyrin\u2010interacting proteins identified rare mutations in a small number of patients, suggesting the possibility of digenic inheritance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our data underscore the existence of a significant subset of FMF patients who are carriers of only 1 <jats:italic>MEFV<\/jats:italic> mutation and demonstrate that complete <jats:italic>MEFV<\/jats:italic> sequencing is not likely to yield a second mutation. Screening for the set of the most common mutations and detection of a single mutation appears to be sufficient in the presence of clinical symptoms for the diagnosis of FMF and the initiation of a trial of colchicine.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.24569","type":"journal-article","created":{"date-parts":[[2009,5,28]],"date-time":"2009-05-28T11:35:01Z","timestamp":1243510501000},"page":"1851-1861","source":"Crossref","is-referenced-by-count":235,"title":["Familial mediterranean fever with a single <i>MEFV<\/i> mutation: Where is the second hit?"],"prefix":"10.1002","volume":"60","author":[{"given":"Matthew G.","family":"Booty","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae Jin","family":"Chae","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seth 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