{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T05:31:25Z","timestamp":1778045485805,"version":"3.51.4"},"reference-count":28,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,2,21]],"date-time":"2023-02-21T00:00:00Z","timestamp":1676937600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["R01 DE28300"],"award-info":[{"award-number":["R01 DE28300"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>To date, there are over 320 variants identified in the <jats:italic>IRF6<\/jats:italic> gene that cause Van der Woude syndrome or popliteal pterygium syndrome. We sequenced this gene in a South African orofacial cleft cohort to identify the causal <jats:italic>IRF6<\/jats:italic> variants in our population.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>Saliva samples from 100 patients with syndromic and non\u2010syndromic CL\u2009\u00b1\u2009P were collected. Patients were recruited from the cleft clinics at two public, tertiary hospitals in Durban, South Africa (SA), namely Inkosi Albert Luthuli Central Hospital (IALCH) and KwaZulu\u2010Natal Children's Hospital (KZNCH). We prospectively sequenced the exons of <jats:italic>IRF6<\/jats:italic> in 100 orofacial cleft cases, and where possible, we also sequenced the parents of the individuals to determine the segregation pattern.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Two variants were identified; one novel (p.Cys114Tyr) and one known (p.Arg84His) missense variant in <jats:italic>IRF6<\/jats:italic> gene were identified. The patient with the p.Cys114Tyr variant was non\u2010syndromic with no clinical VWS phenotype expected of individuals with <jats:italic>IRF6<\/jats:italic> coding variants, and the patient with the p.Arg84His had phenotypic features of popliteal pterygium syndrome. The p.Arg84His variant segregated in the family, with the father also being affected.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study provides evidence that <jats:italic>IRF6<\/jats:italic> variants are found in the South African population. Genetic counselling is essential for affected families, particularly in the absence of a known clinical phenotype since it helps with the plans for future pregnancies.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.2138","type":"journal-article","created":{"date-parts":[[2023,2,22]],"date-time":"2023-02-22T04:44:30Z","timestamp":1677041070000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Novel <i>IRF6<\/i> variant in orofacial cleft patients from Durban, South Africa"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7146-7159","authenticated-orcid":false,"given":"Thirona","family":"Naicker","sequence":"first","affiliation":[{"name":"Genetics, Department of Paediatrics University of KwaZulu\u2010Natal  Durban South Africa"},{"name":"Smile Train Partner  New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9176-0221","authenticated-orcid":false,"given":"Azeez","family":"Alade","sequence":"additional","affiliation":[{"name":"Department of Oral Pathology, Radiology and Medicine, College of Dentistry University of Iowa  Iowa City Iowa USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chinyere","family":"Adeleke","sequence":"additional","affiliation":[{"name":"Department of Oral Pathology, Radiology and Medicine, College of Dentistry University of Iowa  Iowa City Iowa USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter A.","family":"Mossey","sequence":"additional","affiliation":[{"name":"Department of Orthodontics University of Dundee  Dundee UK"},{"name":"Smile Train Global Medical Advisory Board  USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Waheed A.","family":"Awotoye","sequence":"additional","affiliation":[{"name":"Department of Oral Pathology, Radiology and Medicine, College of Dentistry University of Iowa  Iowa City Iowa 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 Iowa USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Oral Pathology, Radiology and Medicine, College of Dentistry University of Iowa  Iowa City Iowa USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joy","family":"Olotu","sequence":"additional","affiliation":[{"name":"Department of Anatomy University of Port Harcourt  Port Harcourt Nigeria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Colleen","family":"Aldous","sequence":"additional","affiliation":[{"name":"School of Clinical Medicine University of KwaZulu\u2010Natal  Durban South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1229-5964","authenticated-orcid":false,"given":"Azeez","family":"Butali","sequence":"additional","affiliation":[{"name":"Department of Oral Pathology, Radiology and Medicine, College of Dentistry University of Iowa  Iowa City Iowa USA"},{"name":"Smile Train Research and Innovation Advisory Council  USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,2,21]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.272"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth0410\u2010248"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.1355"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.32219"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.66"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/GIM.0b013e318197a49a"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkp215"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1159\/000313786"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.273"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320050203"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng985"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bty897"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2009.86"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12675"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2012.141"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33338"},{"key":"e_1_2_11_18_1","unstructured":"Mossey P. 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