{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T22:56:46Z","timestamp":1773269806815,"version":"3.50.1"},"reference-count":54,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2007,12,30]],"date-time":"2007-12-30T00:00:00Z","timestamp":1198972800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2008,2]]},"abstract":"<jats:p>Familial Mediterranean Fever (FMF) is an autosomal, recessively inherited disease, characterized by recurrent and short attacks of fever with serosal inflammation that are caused by mutations in <jats:italic>MEFV <\/jats:italic>gene that encodes pyrin protein. To date, more than 70 disease\u2010associated mutations have been identified, almost all of them representing missense nucleotide changes. FMF is very common among patients with Mediterranean ancestry, although the exact prevalence is not yet known, Greeks are considered to be at \u2018intermediate risk\u2019. In the present study, we studied FMF patients in natives of Crete, a population sharing a common genetic and cultural background. The spectrum of <jats:italic>MEFV <\/jats:italic>gene mutations in 71 patients as well as 158 healthy controls was studied by performing a molecular analysis focused on the 12 most frequent FMF\u2010associated mutations. We found that 59 of 71 (83.1%) FMF patients had at least one <jats:italic>MEFV <\/jats:italic>mutation, five patients were homozygotes and 54 heterozygotes for FMF\u2010associated mutations. No mutations were detected in 12 patients (16.9%). As in high\u2010risk populations, common <jats:italic>MEFV <\/jats:italic>mutations were found in Cretan FMF patients, with the M694V being the most penetrant. M694V and M694I mutations were associated with severe phenotypes, with many patients presenting with uncommon clinical manifestations such as erysipelas\u2010like erythema or renal disturbances. Of interest, 20 (37%) of our heterozygous FMF patients presented with a severe phenotype. Population genetics analysis showed an FMF carrier frequency in healthy Cretan population of approximately 6% (1:17) and places Cretans closer to the Western rather than Eastern populations of the Mediterranean basin. Finally, we constructed a three\u2010dimensional model showing the interaction of the PRYSPRY domain of pyrin with caspase\u20101 onto which we mapped <jats:italic>MEFV <\/jats:italic>mutations, classified according to disease severity. In this model, the \u2018flexible loops\u2019 of caspase\u20101 appear to have no access to some positions that have been previously associated with mild disease, suggesting that alternative pathogenic pathways leading to FMF need to be explored.<\/jats:p>","DOI":"10.1111\/j.1399-0004.2007.00948.x","type":"journal-article","created":{"date-parts":[[2009,1,23]],"date-time":"2009-01-23T10:24:17Z","timestamp":1232706257000},"page":"152-159","source":"Crossref","is-referenced-by-count":27,"title":["Familial Mediterranean Fever in Crete: a genetic and structural biological approach in a population of \u2018intermediate risk\u2019"],"prefix":"10.1111","volume":"73","author":[{"given":"E","family":"Fragouli","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E","family":"Eliopoulos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E","family":"Petraki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P","family":"Sidiropoulos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I","family":"Aksentijevich","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E","family":"Galanakis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H","family":"Kritikos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Repa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G","family":"Fragiadakis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"DT","family":"Boumpas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"GN","family":"Goulielmos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2007,12,30]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(67)90167-2"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.bor.0000198006.65697.5b"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/qjmed\/93.4.223"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1097\/00002281-200301000-00011"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0997-25"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80539-5"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/85893"},{"key":"e_1_2_6_9_2","doi-asserted-by":"crossref","unstructured":"SchanerPE GumucioDL.Familial Mediterranean fever in the post\u2010genomic era: how an ancient disease is providing new insights into inflammatory pathways. 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