{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T21:46:02Z","timestamp":1781300762247,"version":"3.54.1"},"reference-count":16,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2017,8,2]],"date-time":"2017-08-02T00:00:00Z","timestamp":1501632000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"MPP (Medical Practice Plan at the American University of Beirut-Medical Center)"},{"name":"URB (University Research Board at the American University of Beirut)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2017,11]]},"abstract":"<jats:p>Erythropoietic protoporphyria (<jats:styled-content style=\"fixed-case\">EPP<\/jats:styled-content>) is a rare cutaneous and systemic disease caused by mutations in the ferrochelatase gene (<jats:italic><jats:styled-content style=\"fixed-case\">FECH<\/jats:styled-content><\/jats:italic>). The molecular underpinnings of <jats:styled-content style=\"fixed-case\">EPP<\/jats:styled-content> in Middle Eastern populations and relative to other ethnic groups secondary to increased consanguinity are unknown. To understand the molecular pathogenesis of Middle Eastern <jats:styled-content style=\"fixed-case\">EPP<\/jats:styled-content>, we surveyed clinicopathological and molecular features in 6 large consanguineous families from Lebanon and Syria presenting with cutaneous and systemic features consistent with <jats:styled-content style=\"fixed-case\">EPP<\/jats:styled-content>. We observed 30% increased liver disease and 20% elevated end\u2010stage liver complications in our <jats:styled-content style=\"fixed-case\">EPP<\/jats:styled-content> cohort compared to <jats:styled-content style=\"fixed-case\">EPP<\/jats:styled-content> patients previously reported elsewhere. In addition, Middle Eastern <jats:styled-content style=\"fixed-case\">EPP<\/jats:styled-content> patients in our cohort exhibited uniquely an increased incidence of colon cancer. Sequence analysis revealed 2 novel non\u2010synonymous <jats:italic><jats:styled-content style=\"fixed-case\">FECH<\/jats:styled-content><\/jats:italic> mutations in the studied families designated p.<jats:styled-content style=\"fixed-case\">M294T<\/jats:styled-content> and p.<jats:styled-content style=\"fixed-case\">I230M<\/jats:styled-content>. In addition, <jats:styled-content style=\"fixed-case\">FECH<\/jats:styled-content> activity was significantly decreased (6%) in fibroblasts obtained from sun\u2010exposed sites in a patient with p.<jats:styled-content style=\"fixed-case\">M294T<\/jats:styled-content> mutation, whereas in sharp contrast, protected sites from the same patient exhibited 54% activity for the gene. We also found that sun\u2010exposed fibroblasts, relative to sun\u2010protected and control fibroblasts, exhibited suppressed growth and atypical morphology in vitro, and that these effects were alleviated when the cells were co\u2010cultured with sun\u2010protected fibroblasts. Our findings on the increased incidence of colon cancer in <jats:styled-content style=\"fixed-case\">EPP<\/jats:styled-content> patients prompted us to survey <jats:styled-content style=\"fixed-case\">FECH<\/jats:styled-content> expression patterns in cancer. Using publicly available microarray datasets we found that <jats:styled-content style=\"fixed-case\">FECH mRNA<\/jats:styled-content> was largely significantly decreased in colon adenocarcinomas relative to normal colon tissues. Our findings suggest that families with autosomal recessive <jats:styled-content style=\"fixed-case\">EPP<\/jats:styled-content> should be screened more extensively for systemic involvement including liver diseases and colon cancer, and point to a previously unknown yet plausible tumor suppressor role for <jats:styled-content style=\"fixed-case\">FECH<\/jats:styled-content> in colon malignancy.<\/jats:p>","DOI":"10.1111\/cge.12968","type":"journal-article","created":{"date-parts":[[2017,1,11]],"date-time":"2017-01-11T11:05:29Z","timestamp":1484132729000},"page":"495-502","source":"Crossref","is-referenced-by-count":5,"title":["Erythropoietic protoporphyria a clinical and molecular study from Lebanon: Ferrochelatase a potential tumor suppressor gene in colon cancer"],"prefix":"10.1111","volume":"92","author":[{"given":"H.","family":"Kadara","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics American University of Beirut  Beirut Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Nemer","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics American University of Beirut  Beirut Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Safi","sequence":"additional","affiliation":[{"name":"Department of Dermatology American University of Beirut  Beirut Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Rebeiz","sequence":"additional","affiliation":[{"name":"Department of Dermatology American University of Beirut  Beirut Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Daou","sequence":"additional","affiliation":[{"name":"Department of Pathology American University of Beirut  Beirut Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Delbani","sequence":"additional","affiliation":[{"name":"Department of Dermatology American University of Beirut  Beirut Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W.","family":"Btadini","sequence":"additional","affiliation":[{"name":"Department of Dermatology American University of Beirut  Beirut Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"O.","family":"Abbas","sequence":"additional","affiliation":[{"name":"Department of Dermatology American University of Beirut  Beirut Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Tofaili","sequence":"additional","affiliation":[{"name":"Department of Dermatology American University of Beirut  Beirut Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Bitar","sequence":"additional","affiliation":[{"name":"Department of Pediatrics American University of Beirut  Beirut 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