{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T14:00:19Z","timestamp":1768831219366,"version":"3.49.0"},"reference-count":37,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2018,3,7]],"date-time":"2018-03-07T00:00:00Z","timestamp":1520380800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["PNPD\/CAPES n\u00ba 2250\/2011"],"award-info":[{"award-number":["PNPD\/CAPES n\u00ba 2250\/2011"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Laboratory Analysis"],"published-print":{"date-parts":[[2018,7]]},"abstract":"Background<\/jats:title>Although more than 14 loci may be involved in the development of nonsyndromic cleft lip and palate (NSCLP<\/jats:styled-content>), the etiology has not been fully elucidated due to genetic and environmental risk factor interactions. Despite advances in identifying genes associated with the NSCLP<\/jats:styled-content> development using traditional genetic mapping strategies of candidate genes, genome\u2010wide studies, and epidemiologic and linkage analysis, microarray techniques have become important complementary tools in the search for potential causative oral clefts genes in genetic studies. Microarray hybridization enables scanning of the whole genome and detecting copy number variants (CNV<\/jats:styled-content>s). Although common benign CNV<\/jats:styled-content>s are often smaller, with sizes smaller than 20\u00a0kb, here we reveal small exonic CNV<\/jats:styled-content>s based on the importance of the encompassed genes in cleft lip and palate phenotype.<\/jats:p><\/jats:sec>Methods<\/jats:title>Microarray hybridization analysis was performed in 15 individuals with NSCLP<\/jats:styled-content>.<\/jats:p><\/jats:sec>Results<\/jats:title>We identified 11 exonic CNV<\/jats:styled-content>s affecting at least one exon of the candidate genes. Thirteen candidate genes (COL<\/jats:styled-content>11A1\u2013<\/jats:italic>1p21; IRF<\/jats:styled-content>6\u2013<\/jats:italic>1q32.3; MSX<\/jats:styled-content>1\u2013<\/jats:italic>4p16.2; TERT<\/jats:styled-content><\/jats:italic>\u20135p15.33; MIR<\/jats:styled-content>4457<\/jats:italic>\u20135p15.33; CLPTM<\/jats:styled-content>1L<\/jats:italic>\u20135p15.33; ESR<\/jats:styled-content>1\u2013<\/jats:italic>6q25.1; GLI<\/jats:styled-content>3<\/jats:italic>\u20137p13; FGFR<\/jats:styled-content>\u2013<\/jats:italic>8p11.23; TBX<\/jats:styled-content>1\u2013<\/jats:italic>22q11.21; OFD<\/jats:styled-content>\u2013<\/jats:italic>Xp22; PHF<\/jats:styled-content>8\u2013<\/jats:italic>Xp11.22; and FLNA<\/jats:styled-content>\u2013<\/jats:italic>Xq28) overlapped with the CNV<\/jats:styled-content>s identified.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>Considering the importance to NSCLP<\/jats:styled-content>, the microdeletions that encompass MSX<\/jats:styled-content>1,<\/jats:italic> microduplications over TERT<\/jats:styled-content>, MIR<\/jats:styled-content>4457, CLPTM<\/jats:styled-content>1L,<\/jats:italic> and microduplication of PHF<\/jats:styled-content>8<\/jats:italic> have been identified as small CNV<\/jats:styled-content>s related to sequence variants associated with oral clefts susceptibility. Our findings represent a preliminary study on the clinical significance of small CNV<\/jats:styled-content>s and their relationship with genes implicated in NSCLP<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcla.22428","type":"journal-article","created":{"date-parts":[[2018,3,7]],"date-time":"2018-03-07T07:36:37Z","timestamp":1520408197000},"source":"Crossref","is-referenced-by-count":12,"title":["Application of high\u2010resolution array platform for genome\u2010wide copy number variation analysis in patients with nonsyndromic cleft lip and palate"],"prefix":"10.1002","volume":"32","author":[{"given":"Heglayne Pereira Vital","family":"da Silva","sequence":"first","affiliation":[{"name":"Department of Clinical and Toxicological Analyses Federal University of Rio Grande do Norte Natal Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gustavo Henrique de Medeiros","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Department of Clinical and Toxicological Analyses Federal University of Rio Grande do Norte Natal Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcela Abbott Galv\u00e3o","family":"Ururahy","sequence":"additional","affiliation":[{"name":"Department of Clinical and Toxicological Analyses Federal University of Rio Grande do Norte Natal Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jo\u00e3o Felipe","family":"Bezerra","sequence":"additional","affiliation":[{"name":"Department of Clinical and Toxicological Analyses Federal University of Rio Grande do Norte Natal Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karla Simone Costa","family":"de Souza","sequence":"additional","affiliation":[{"name":"Department of Clinical and Toxicological Analyses Federal University of Rio Grande do Norte Natal Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raul Hernandes","family":"Bortolin","sequence":"additional","affiliation":[{"name":"Department of Clinical and Toxicological Analyses Federal University of Rio Grande do Norte Natal Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andr\u00e9 Ducati","family":"Luchessi","sequence":"additional","affiliation":[{"name":"Department of Clinical and Toxicological Analyses Federal University of Rio Grande do Norte Natal Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9252-0278","authenticated-orcid":false,"given":"Vivian Nogueira","family":"Silbiger","sequence":"additional","affiliation":[{"name":"Department of Clinical and Toxicological Analyses Federal University of Rio Grande do Norte Natal Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Val\u00e9ria Morgiana Gualberto Duarte Moreira","family":"Lima","sequence":"additional","affiliation":[{"name":"Department of Clinical and Toxicological Analyses Federal University of Rio Grande do Norte Natal Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gisele Correia Pacheco","family":"Leite","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Federal University of Rio Grande do Norte Natal Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Edinilma Felinto","family":"Brito","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Federal University of Rio Grande do Norte Natal Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erlane Marques","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Medical Genetics Service Albert Sabin Children's Hospital Fortaleza Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vera L\u00facia","family":"Gil\u2010da\u2010Silva\u2010Lopes","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Faculty of Medical Sciences University of Campinas Campinas S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2452-4047","authenticated-orcid":false,"given":"Adriana Augusto","family":"de Rezende","sequence":"additional","affiliation":[{"name":"Department of Clinical and Toxicological Analyses Federal University of Rio Grande do Norte Natal Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,3,7]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.4103\/0973-029X.99074"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)60695-4"},{"key":"e_1_2_6_4_1","first-page":"167","article-title":"Cleft lip and palate. 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