{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T17:06:19Z","timestamp":1778519179079,"version":"3.51.4"},"reference-count":51,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2021,6,21]],"date-time":"2021-06-21T00:00:00Z","timestamp":1624233600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100006545","name":"National Institute on Minority Health and Health Disparities","doi-asserted-by":"publisher","award":["S21 MD001830"],"award-info":[{"award-number":["S21 MD001830"]}],"id":[{"id":"10.13039\/100006545","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006545","name":"National Institute on Minority Health and Health Disparities","doi-asserted-by":"publisher","award":["U54 MD007587"],"award-info":[{"award-number":["U54 MD007587"]}],"id":[{"id":"10.13039\/100006545","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["R00 DE022378"],"award-info":[{"award-number":["R00 DE022378"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["R01DE028300"],"award-info":[{"award-number":["R01DE028300"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["R00 DE024571"],"award-info":[{"award-number":["R00 DE024571"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["R03 DE024776"],"award-info":[{"award-number":["R03 DE024776"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oral Diseases"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>\n                      Cleft lip with\/without cleft palate and cleft palate only is congenital birth defects where the upper lip and\/or palate fail to fuse properly during embryonic facial development. Affecting ~1.2\/1000\u00a0live births worldwide, these orofacial clefts impose significant social and financial burdens on affected individuals and their families. Orofacial clefts have a complex etiology resulting from genetic variants combined with environmental covariates. Recent genome\u2010wide association studies and whole\u2010exome sequencing for orofacial clefts identified significant genetic associations and variants in several genes. Of these, we investigated the role of common\/rare variants in\n                      <jats:italic>SHH<\/jats:italic>\n                      ,\n                      <jats:italic>RORA<\/jats:italic>\n                      ,\n                      <jats:italic>MRPL53<\/jats:italic>\n                      ,\n                      <jats:italic>ACVR1<\/jats:italic>\n                      , and\n                      <jats:italic>GDF11<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>We sequenced these five genes in 1255 multi\u2010ethnic cleft lip with\/without palate and cleft palate only samples in order to find variants that may provide potential explanations for the missing heritability of orofacial clefts. Rare and novel variants were further analyzed using in silico predictive tools.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Ninteen total variants of interest were found, with variant types including stop\u2010gain, missense, synonymous, intronic, and splice\u2010site variants. Of these, 3 novel missense variants were found, one in\n                      <jats:italic>SHH<\/jats:italic>\n                      , one in\n                      <jats:italic>RORA<\/jats:italic>\n                      , and one in\n                      <jats:italic>GDF11<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This study provides evidence that variants in\n                      <jats:italic>SHH<\/jats:italic>\n                      ,\n                      <jats:italic>RORA<\/jats:italic>\n                      ,\n                      <jats:italic>MRPL53<\/jats:italic>\n                      ,\n                      <jats:italic>ACVR1<\/jats:italic>\n                      , and\n                      <jats:italic>GDF11<\/jats:italic>\n                      may contribute to risk of orofacial clefts in various populations.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/odi.13932","type":"journal-article","created":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T21:30:09Z","timestamp":1622583009000},"page":"1921-1935","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Variant analyses of candidate genes in orofacial clefts in multi\u2010ethnic populations"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6801-1177","authenticated-orcid":false,"given":"Mary","family":"Li","sequence":"first","affiliation":[{"name":"Department of Oral Pathology, Radiology and Medicine College of Dentistry University of Iowa Iowa City IA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joy","family":"Olotu","sequence":"additional","affiliation":[{"name":"Department of Anatomy University of Health Sciences University of Port Harcourt Choba Nigeria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmen J.","family":"Buxo\u2010Martinez","sequence":"additional","affiliation":[{"name":"Dental and Craniofacial Genomics Core University of Puerto Rico School of Dental Medicine San Juan PR USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter A.","family":"Mossey","sequence":"additional","affiliation":[{"name":"Department of Orthodontics University of Dundee Dundee UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deepti","family":"Anand","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences University of Delaware Newark DE USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tamara","family":"Busch","sequence":"additional","affiliation":[{"name":"Department of Oral Pathology, Radiology and Medicine College of Dentistry University of Iowa Iowa City IA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Azeez","family":"Alade","sequence":"additional","affiliation":[{"name":"Department of Oral Pathology, Radiology and Medicine College of Dentistry University of Iowa Iowa City IA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0080-9101","authenticated-orcid":false,"given":"Lord J. 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