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Karola Marcinkowskiego w Poznaniu","doi-asserted-by":"publisher","award":["502-14-11241820-41286"],"award-info":[{"award-number":["502-14-11241820-41286"]}],"id":[{"id":"10.13039\/501100010438","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004281","name":"Narodowe Centrum Nauki","doi-asserted-by":"publisher","award":["2012\/07\/B\/NZ2\/00115"],"award-info":[{"award-number":["2012\/07\/B\/NZ2\/00115"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oral Diseases"],"published-print":{"date-parts":[[2019,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>The etiology of non\u2010syndromic cleft lip with or without cleft palate (nsCL\/P) is multifactorial, heterogeneous, and still not completely understood. The aim of the present study was to examine the associations between common and rare<jats:italic>PAX7<\/jats:italic>nucleotide variants and the risk of this common congenital anomaly in a Polish population.<\/jats:p><\/jats:sec><jats:sec><jats:title>Subjects and methods<\/jats:title><jats:p>Eight top nsCL\/P\u2010associated<jats:italic>PAX<\/jats:italic>7 variants identified in our cleft genome\u2010wide association study (GWAS) were selected for replication analysis in an independent group of patients and controls (<jats:italic>n<\/jats:italic>\u00a0=\u00a0247 and<jats:italic>n<\/jats:italic>\u00a0=\u00a0445, respectively). In addition, mutation screening of the<jats:italic>PAX7<\/jats:italic>protein\u2010coding region was conducted.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Analysis of the pooled data from the GWAS and replication study confirmed that common<jats:italic>PAX7<\/jats:italic>nucleotide variants are significantly associated with the increased risk of nsCL\/P. The strongest individual variant was rs1339062 (c.586\u00a0+\u00a015617T\u00a0&gt;\u00a0C) with a<jats:italic>p<\/jats:italic>\u2010value\u00a0=\u00a02.47E\u221205 (OR\u00a0=\u00a01.4, 95%CI: 1.20\u20131.64). Sequencing analysis identified a novel synonymous<jats:italic>PAX7<\/jats:italic>substitution (c.87G\u00a0&gt;\u00a0A, p.Val29Val) in a single patient with nsCLP. This transition located in the early exonic position was predicted to disrupt potential splice enhancer elements.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our study confirmed that<jats:italic>PAX7<\/jats:italic>is a strong candidate gene for nsCL\/P. Nucleotide variants of this gene contribute to the etiology of nsCL\/P in the homogenous Polish population.<\/jats:p><\/jats:sec>","DOI":"10.1111\/odi.13139","type":"journal-article","created":{"date-parts":[[2019,6,7]],"date-time":"2019-06-07T14:20:14Z","timestamp":1559917214000},"page":"1608-1618","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["<i>PAX7<\/i>nucleotide variants and the risk of non\u2010syndromic orofacial clefts in the Polish population"],"prefix":"10.1111","volume":"25","author":[{"given":"Agnieszka","family":"Gaczkowska","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Poznan University of Medical Sciences Poznan Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Biedziak","sequence":"additional","affiliation":[{"name":"Clinic of Craniofacial Anomalies Poznan University of Medical Sciences Poznan Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margareta","family":"Budner","sequence":"additional","affiliation":[{"name":"Eastern Poland Burn Treatment and Reconstructive Center Leczna Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ma\u0142gorzata","family":"Zadurska","sequence":"additional","affiliation":[{"name":"Department of Orthodontics Medical University of Warsaw Warsaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnieszka","family":"Lasota","sequence":"additional","affiliation":[{"name":"Department of Jaw Orthopedics Medical University of Lublin Lublin Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamil K.","family":"Hozyasz","sequence":"additional","affiliation":[{"name":"Institute of Health Sciences State School of Higher Education Biala Podlaska Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justyna","family":"D\u0105browska","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Poznan University of Medical Sciences Poznan Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"W\u00f3jcicki","sequence":"additional","affiliation":[{"name":"Plastic Surgery Clinic Medical University in Wroclaw Wroclaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Szponar\u2010\u017burowska","sequence":"additional","affiliation":[{"name":"Clinic of Craniofacial Anomalies Poznan University of Medical Sciences Poznan Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kacper","family":"\u017bukowski","sequence":"additional","affiliation":[{"name":"Department of Cattle Breeding National Research Institute of Animal Production Balice Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pawe\u0142 P.","family":"Jagodzi\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Poznan University of Medical Sciences Poznan Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4181-9402","authenticated-orcid":false,"given":"Adrianna","family":"Mostowska","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Poznan University of Medical Sciences Poznan Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,6,25]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/tera.1420430205"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0041-008X(89)90096-3"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1004(1996)7:1<30::AID-HUMU4>3.0.CO;2-T"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/jez.1401270206"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1204599"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.580"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-013-1283-6"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.23.13164"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwi132"},{"issue":"10","key":"e_1_2_8_11_1","doi-asserted-by":"crossref","first-page":"2545","DOI":"10.1002\/ajmg.a.36141","article-title":"Analysis of susceptibility loci for nonsyndromic orofacial clefting in a European trio sample","volume":"161","author":"B\u00f6hmer A. 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