{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T14:15:36Z","timestamp":1792592136379,"version":"4.5.0"},"reference-count":81,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,3,4]],"date-time":"2023-03-04T00:00:00Z","timestamp":1677888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Social Fund and Wielkopolska Voivodeship (Regional Operational Programme for Wielkopolskie Voivodeship 2014-2020)","award":["RPWP.07.02.02-30-0037\/16"],"award-info":[{"award-number":["RPWP.07.02.02-30-0037\/16"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Non-syndromic cleft palate (ns-CP) has a genetically heterogeneous aetiology. Numerous studies have suggested a crucial role of rare coding variants in characterizing the unrevealed component of genetic variation in ns-CP called the \u201cmissing heritability\u201d. Therefore, this study aimed to detect low-frequency variants that are implicated in ns-CP aetiology in the Polish population. For this purpose, coding regions of 423 genes associated with orofacial cleft anomalies and\/or involved with facial development were screened in 38 ns-CP patients using the next-generation sequencing technology. After multistage selection and prioritisation, eight novel and four known rare variants that may influence an individual\u2019s risk of ns-CP were identified. Among detected alternations, seven were located in novel candidate genes for ns-CP, including COL17A1 (c.2435-1G&gt;A), DLG1 (c.1586G&gt;C, p.Glu562Asp), NHS (c.568G&gt;C, p.Val190Leu\u2014de novo variant), NOTCH2 (c.1997A&gt;G, p.Tyr666Cys), TBX18 (c.647A&gt;T, p.His225Leu), VAX1 (c.400G&gt;A, p.Ala134Thr) and WNT5B (c.716G&gt;T, p.Arg239Leu). The remaining risk variants were identified within genes previously linked to ns-CP, confirming their contribution to this anomaly. This list included ARHGAP29 (c.1706G&gt;A, p.Arg569Gln), FLNB (c.3605A&gt;G, Tyr1202Cys), IRF6 (224A&gt;G, p.Asp75Gly\u2014de novo variant), LRP6 (c.481C&gt;A, p.Pro161Thr) and TP63 (c.353A&gt;T, p.Asn118Ile). In summary, this study provides further insights into the genetic components contributing to ns-CP aetiology and identifies novel susceptibility genes for this craniofacial anomaly.<\/jats:p>","DOI":"10.3390\/jcm12052051","type":"journal-article","created":{"date-parts":[[2023,3,6]],"date-time":"2023-03-06T02:06:43Z","timestamp":1678068403000},"page":"2051","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Identification of Novel Risk Variants of Non-Syndromic Cleft Palate by Targeted Gene Panel Sequencing"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2128-3057","authenticated-orcid":false,"given":"Justyna","family":"D\u0105browska","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Poznan University of Medical Sciences, 6 Swiecickiego Street, 60-781 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Biedziak","sequence":"additional","affiliation":[{"name":"Department of Orthodontics and Craniofacial Anomalies, Poznan University of Medical Sciences, 60-812 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnieszka","family":"Bogdanowicz","sequence":"additional","affiliation":[{"name":"Department of Orthodontics and Craniofacial Anomalies, Poznan University of Medical Sciences, 60-812 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, 6 Swiecickiego Street, 60-781 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.1016\/S0140-6736(09)60695-4","article-title":"Cleft Lip and Palate","volume":"374","author":"Mossey","year":"2009","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1136\/bmj.38106.559120.7C","article-title":"Long term follow up study of survival associated with cleft lip and palate at birth","volume":"328","author":"Christensen","year":"2004","journal-title":"BMJ"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/j.1601-0825.2009.01588.x","article-title":"The impact of orofacial clefts on quality of life and healthcare use and costs","volume":"16","author":"Wehby","year":"2010","journal-title":"Oral Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1038\/sj.bjc.6600488","article-title":"Do parents of children with congenital malformations have a higher cancer risk? A nationwide study in Denmark","volume":"87","author":"Zhu","year":"2002","journal-title":"Br. J. Cancer"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/j.molmed.2011.07.007","article-title":"Breakthroughs in the genetics of orofacial clefting","volume":"17","author":"Mangold","year":"2011","journal-title":"Trends Mol. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"14364","DOI":"10.1038\/ncomms14364","article-title":"Genome-wide analyses of non-syndromic cleft lip with palate identify 14 novel loci and genetic heterogeneity","volume":"8","author":"Yu","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1242\/dev.103.Supplement.41","article-title":"Palate Development","volume":"103","author":"Ferguson","year":"1988","journal-title":"Development"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1111\/j.1601-0825.2009.01577.x","article-title":"The genetics of isolated orofacial clefts: From genotypes to subphenotypes","volume":"15","author":"Jugessur","year":"2009","journal-title":"Oral Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1002\/ajmg.c.31381","article-title":"Genetics of cleft lip and cleft palate","volume":"163","author":"Leslie","year":"2013","journal-title":"Am. J. Med. Genet. Part C Semin. Med. Genet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.cps.2013.12.003","article-title":"Classification, Epidemiology, and Genetics of Orofacial Clefts","volume":"41","author":"Watkins","year":"2014","journal-title":"Clin. Plast. Surg."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1038\/nrg2933","article-title":"Cleft lip and palate: Understanding genetic and environmental influences","volume":"12","author":"Dixon","year":"2011","journal-title":"Nat. Rev. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1034\/j.1399-0004.2002.610402.x","article-title":"Gene\/environment causes of cleft lip and\/or palate","volume":"61","author":"Murray","year":"2002","journal-title":"Clin. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1177\/0022034516657003","article-title":"Association Studies and Direct DNA Sequencing Implicate Genetic Susceptibility Loci in the Etiology of Nonsyndromic Orofacial Clefts in Sub-Saharan African Populations","volume":"95","author":"Gowans","year":"2016","journal-title":"J. Dent. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1002\/bdr2.1213","article-title":"Nonsyndromic Cleft Palate: An Association Study at GWAS Candidate Loci in a Multiethnic Sample","volume":"110","author":"Ishorst","year":"2018","journal-title":"Birth Defects Res."},{"key":"ref_15","first-page":"469","article-title":"Evidence for gene-environment interaction in a genome wide study of nonsyndromic cleft palate","volume":"35","author":"Beaty","year":"2011","journal-title":"Genet. Epidemiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1016\/j.ajhg.2016.02.014","article-title":"A Genome-Wide Association Study of Nonsyndromic Cleft Palate Identifies an Etiologic Missense Variant in GRHL3","volume":"98","author":"Leslie","year":"2016","journal-title":"Am. J. Hum. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1093\/hmg\/ddy402","article-title":"Genomic analyses in African populations identify novel risk loci for cleft palate","volume":"28","author":"Butali","year":"2019","journal-title":"Hum. Mol. Genet."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Huang, L., Jia, Z., Shi, Y., Du, Q., Shi, J., Wang, Z., Mou, Y., Wang, Q., Zhang, B., and Wang, Q. (2019). Genetic factors define CPO and CLO subtypes of nonsyndromicorofacial cleft. PLoS Genet., 15.","DOI":"10.1371\/journal.pgen.1008357"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1177\/0022034520943867","article-title":"Genome-wide Analyses Identify a Novel Risk Locus for Nonsyndromic Cleft Palate","volume":"99","author":"He","year":"2020","journal-title":"J. Dent. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1016\/j.ajhg.2016.02.013","article-title":"Sequencing the GRHL3 Coding Region Reveals Rare Truncating Mutations and a Common Susceptibility Variant for Nonsyndromic Cleft Palate","volume":"98","author":"Mangold","year":"2016","journal-title":"Am. J. Hum. Genet."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"592271","DOI":"10.3389\/fcell.2020.592271","article-title":"Non-syndromic Cleft Palate: An Overview on Human Genetic and Environmental Risk Factors","volume":"8","author":"Martinelli","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1002\/ajmg.a.61183","article-title":"Accumulation of rare coding variants in genes implicated in risk of human cleft lip with or without cleft palate","volume":"179","author":"Marini","year":"2019","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.1002\/ajmg.a.38210","article-title":"Association studies of low-frequency coding variants in nonsyndromic cleft lip with or without cleft palate","volume":"173","author":"Leslie","year":"2017","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"638522","DOI":"10.3389\/fcell.2021.638522","article-title":"Identification of Novel Variants in Cleft Palate-Associated Genes in Brazilian Patients With Non-syndromic Cleft Palate Only","volume":"9","author":"Machado","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1534\/genetics.114.165225","article-title":"Whole Exome Sequencing of Distant Relatives in Multiplex Families Implicates Rare Variants in Candidate Genes for Oral Clefts","volume":"197","author":"Bureau","year":"2014","journal-title":"Genetics"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1136\/jmedgenet-2017-105110","article-title":"Whole exome sequencing identifies mutations in 10% of patients with familial non-syndromic cleft lip and\/or palate in genes mutated in well-known syndromes","volume":"55","author":"Basha","year":"2018","journal-title":"J. Med. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1314","DOI":"10.1177\/0022034517722761","article-title":"Candidate Genes for Nonsyndromic Cleft Palate Detected by Exome Sequencing","volume":"96","author":"Hoebel","year":"2017","journal-title":"J. Dent. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1002\/bdra.23596","article-title":"Exome sequencing provides additional evidence for the involvement ofARHGAP29in Mendelian orofacial clefting and extends the phenotypic spectrum to isolated cleft palate","volume":"109","author":"Liu","year":"2017","journal-title":"Birth Defects Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"30457","DOI":"10.1038\/srep30457","article-title":"Deleterious coding variants in multi-case families with non-syndromic cleft lip and\/or palate phenotypes","volume":"6","author":"Pengelly","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e700","DOI":"10.20883\/medical.e700","article-title":"Publication Ethics of Human Studies in the Light of the Declaration of Helsinki\u2014A Mini-Review","volume":"91","author":"Guzik","year":"2022","journal-title":"J. Med. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1007\/s00438-022-01919-w","article-title":"Identification of Novel Susceptibility Genes for Non-Syndromic Cleft Lip with or without Cleft Palate Using NGS-Based Multigene Panel Testing","volume":"297","author":"Biedziak","year":"2022","journal-title":"Mol. Genet. Genomics"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Biedziak, B., Firlej, E., D\u0105browska, J., Bogdanowicz, A., Zadurska, M., and Mostowska, A. (2022). Novel Candidate Genes for Non-Syndromic Tooth Agenesis Identified Using Targeted Next-Generation Sequencing. J. Clin. Med., 11.","DOI":"10.3390\/jcm11206089"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1002\/gepi.22214","article-title":"Identifying Genetic Sources of Phenotypic Heterogeneity in Orofacial Clefts by Targeted Sequencing","volume":"43","author":"Carlson","year":"2017","journal-title":"Genet. Epidemiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1002\/gepi.22214","article-title":"A Systematic Genetic Analysis and Visualization of Phenotypic Heterogeneity among Orofacial Cleft GWAS Signals","volume":"43","author":"Carlson","year":"2019","journal-title":"Genet. Epidemiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.matbio.2018.10.003","article-title":"Amino Acid Substitution in the C-Terminal Domain of Collagen XVII Reduces Laminin-332 Interaction Causing Mild Skin Fragility with Atrophic Scarring","volume":"80","author":"Kroeger","year":"2019","journal-title":"Matrix Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1038\/ijos.2016.56","article-title":"Identification of shared and unique gene families associated with oral clefts","volume":"9","author":"Funato","year":"2017","journal-title":"Int. J. Oral Sci."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Liu, F., van der Lijn, F., Schurmann, C., Zhu, G., Chakravarty, M.M., Hysi, P.G., Wollstein, A., Lao, O., de Bruijne, M., and Ikram, M.A. (2012). A Genome-Wide Association Study Identifies Five Loci Influencing Facial Morphology in Europeans. PLoS Genet., 8.","DOI":"10.1371\/journal.pgen.1002932"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Feng, W., Leach, S.M., Tipney, H., Phang, T., Geraci, M., Spritz, R.A., Hunter, L.E., and Williams, T. (2009). Spatial and Temporal Analysis of Gene Expression during Growth and Fusion of the Mouse Facial Prominences. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0008066"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/ng.506","article-title":"Genome-wide association study identifies two susceptibility loci for nonsyndromic cleft lip with or without cleft palate","volume":"42","author":"Mangold","year":"2010","journal-title":"Nat. Genet."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1002\/ajmg.a.35749","article-title":"Replication of Genome Wide Association Identified Candidate Genes Confirm the Role of Common and Rare Variants in PAX7 and VAX1 in the Etiology of Nonsyndromic CL(P)","volume":"161","author":"Butali","year":"2013","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1111\/cge.13141","article-title":"Common Variants in DLG1 Locus Are Associated with Non-Syndromic Cleft Lip with or without Cleft Palate","volume":"93","author":"Mostowska","year":"2018","journal-title":"Clin. Genet."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1002\/gepi.21888","article-title":"Gene-Gene Interaction Among WNT Genes for Oral Cleft in Trios","volume":"39","author":"Li","year":"2015","journal-title":"Genet. Epidemiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2421","DOI":"10.1093\/hmg\/ddq125","article-title":"The Nance\u2013Horan syndrome protein encodes a functional WAVE homology domain (WHD) and is important for co-ordinating actin remodelling and maintaining cell morphology","volume":"19","author":"Brooks","year":"2010","journal-title":"Hum. Mol. Genet."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.1086\/379381","article-title":"Mutations in a Novel Gene, NHS, Cause the Pleiotropic Effects of Nance-Horan Syndrome, Including Severe Congenital Cataract, Dental Anomalies, and Mental Retardation","volume":"73","author":"Burdon","year":"2003","journal-title":"Am. J. Hum. Genet."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"89","DOI":"10.3109\/13816810.2011.634881","article-title":"Phenotype-genotype Correlation in Potential Female Carriers of X-linked Developmental Cataract (Nance-Horan Syndrome)","volume":"33","author":"Khan","year":"2012","journal-title":"Ophthalmic Genet."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.ajhg.2020.05.018","article-title":"Genome-Wide Enrichment of De Novo Coding Mutations in Orofacial Cleft Trios","volume":"107","author":"Bishop","year":"2020","journal-title":"Am. J. Hum. Genet."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.gendis.2020.04.006","article-title":"Notch signaling: Its essential roles in bone and craniofacial development","volume":"8","author":"Pakvasa","year":"2021","journal-title":"Genes Dis."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"4571","DOI":"10.1038\/emboj.2011.325","article-title":"IRF6 is a mediator of Notch pro-differentiation and tumour suppressive function in keratinocytes","volume":"30","author":"Restivo","year":"2011","journal-title":"EMBO J."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1588","DOI":"10.1002\/bdr2.1754","article-title":"Genetics and signaling mechanisms of orofacial clefts","volume":"112","author":"Reynolds","year":"2020","journal-title":"Birth Defects Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"dev174888","DOI":"10.1242\/dev.174888","article-title":"The Molecular Anatomy of Mammalian Upper Lip and Primary Palate Fusion at Single Cell Resolution","volume":"146","author":"Li","year":"2019","journal-title":"Development"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2632","DOI":"10.1093\/hmg\/ddp201","article-title":"Integration of IRF6 and Jagged2 signalling is essential for controlling palatal adhesion and fusion competence","volume":"18","author":"Richardson","year":"2009","journal-title":"Hum. Mol. Genet."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2197","DOI":"10.1002\/humu.23879","article-title":"Alagille syndrome mutation update: Comprehensive overview of JAG1 and NOTCH2 mutation frequencies and insight into missense variant classification","volume":"40","author":"Gilbert","year":"2019","journal-title":"Hum. Mutat."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1136\/jmedgenet-2011-100544","article-title":"NOTCH2mutations in Alagille syndrome","volume":"49","author":"Kamath","year":"2012","journal-title":"J. Med. Genet."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2781","DOI":"10.1002\/ajmg.a.35512","article-title":"Overt Cleft Palate Phenotype and TBX1 Genotype Correlations in Velo-Cardio-Facial\/DiGeorge\/22q11","volume":"158A","author":"Herman","year":"2012","journal-title":"2 Deletion Syndrome Patients. Am. J. Med. Genet. A"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Vieira, A.R., Avila, J.R., Daack-Hirsch, S., Dragan, E., F\u00e9lix, T.M., Rahimov, F., Harrington, J., Schultz, R.R., Watanabe, Y., and Johnson, M. (2005). Medical Sequencing of Candidate Genes for Nonsyndromic Cleft Lip and Palate. PLoS Genet., 1.","DOI":"10.1371\/journal.pgen.0010064"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1002\/bdra.20687","article-title":"Association between genetic variants of reported candidate genes or regions and risk of cleft lip with or without cleft palate in the polish population","volume":"88","author":"Mostowska","year":"2010","journal-title":"Birth Defects Res. Part A Clin. Mol. Teratol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1136\/jmg.2003.010868","article-title":"TBX22 mutations are a frequent cause of cleft palate","volume":"41","author":"Marcano","year":"2004","journal-title":"J. Med. Genet."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1093\/hmg\/ddh052","article-title":"Genetics of Cleft Lip and Palate: Syndromic Genes Contribute to the Incidence of Non-Syndromic Clefts","volume":"13","author":"Stanier","year":"2004","journal-title":"Hum. Mol. Genet."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1534\/genetics.117.300535","article-title":"Identification of Isthmin 1 as a Novel Clefting and Craniofacial Patterning Gene in Humans","volume":"208","author":"Lansdon","year":"2018","journal-title":"Genetics"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/S0925-4773(00)00494-9","article-title":"Cloning and expression analysis of the mouse T-box gene Tbx18","volume":"100","author":"Kraus","year":"2001","journal-title":"Mech. Dev."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1038\/ng1894","article-title":"Irf6 is a key determinant of the keratinocyte proliferation-differentiation switch","volume":"38","author":"Richardson","year":"2006","journal-title":"Nat. Genet."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1002\/bdra.23286","article-title":"Further evidence suggesting a role for variation in ARHGAP29 variants in nonsyndromic cleft lip\/palate","volume":"100","author":"Letra","year":"2014","journal-title":"Birth Defects Res. Part A Clin. Mol. Teratol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1038\/s41431-019-0370-0","article-title":"Deletions and loss-of-function variants in TP63 associated with orofacial clefting","volume":"27","author":"Khandelwal","year":"2019","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Jugessur, A., Shi, M., Gjessing, H.K., Lie, R.T., Wilcox, A.J., Weinberg, C., Christensen, K., Boyles, A.L., Daack-Hirsch, S., and Nguyen, T.T. (2010). Maternal Genes and Facial Clefts in Offspring: A Comprehensive Search for Genetic Associations in Two Population-Based Cleft Studies from Scandinavia. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0011493"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1159\/000337619","article-title":"Wnt Signaling in Lip and Palate Development","volume":"16","author":"He","year":"2012","journal-title":"Front. Oral Biol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.1083\/jcb.134.6.1469","article-title":"Dlg Protein Is Required for Junction Structure, Cell Polarity, and Proliferation Control in Drosophila Epithelia","volume":"134","author":"Woods","year":"1996","journal-title":"J. Cell Biol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"6693","DOI":"10.2741\/3182","article-title":"Role of Lgl\/Dlg\/Scribble in the Regulation of Epithelial Junction, Polarity and Growth","volume":"13","author":"Yamanaka","year":"2008","journal-title":"Front. Biosci."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Iizuka-Kogo, A., Senda, T., Akiyama, T., Shimomura, A., Nomura, R., Hasegawa, Y., Yamamura, K.-I., Kogo, H., Sawai, N., and Matsuzaki, T. (2015). Requirement of DLG1 for Cardiovascular Development and Tissue Elongation during Cochlear, Enteric, and Skeletal Development: Possible Role in Convergent Extension. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0123965"},{"key":"ref_69","first-page":"6693","article-title":"Requirement for Dlgh-1 in Planar Cell Polarity and Skeletogenesis during Vertebrate Development","volume":"134","author":"Seelan","year":"2013","journal-title":"Development"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.1128\/MCB.21.5.1475-1483.2001","article-title":"Craniofacial Dysmorphogenesis Including Cleft Palate in Mice with an Insertional Mutation in the discs large Gene","volume":"21","author":"Caruana","year":"2001","journal-title":"Mol. Cell. Biol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1799","DOI":"10.1242\/dev.02830","article-title":"Abnormal development of urogenital organs in Dlgh1-deficient mice","volume":"134","author":"Ishidao","year":"2007","journal-title":"Development"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1002\/bdra.20720","article-title":"Studies with Wnt Genes and Nonsyndromic Cleft Lip and Palate","volume":"88","author":"Menezes","year":"2010","journal-title":"Birth Defects Res. A Clin. Mol. Teratol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2212","DOI":"10.1093\/hmg\/ddn121","article-title":"Variation in WNT genes is associated with non-syndromic cleft lip with or without cleft palate","volume":"17","author":"Chiquet","year":"2008","journal-title":"Hum. Mol. Genet."},{"key":"ref_74","first-page":"2541","article-title":"Roles of Wnt Pathway Genes Wls, Wnt9a, Wnt5b, Frzb and Gpc4 in Regulating Convergent-Extension during Zebrafish Palate Morphogenesis","volume":"143","author":"Rochard","year":"2016","journal-title":"Development"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"3161","DOI":"10.1242\/dev.037440","article-title":"Lrp6-mediated canonical Wnt signaling is required for lip formation and fusion","volume":"136","author":"Song","year":"2009","journal-title":"Development"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1002\/humu.22750","article-title":"Rare LRP6 Variants Identified in Spina Bifida P atients","volume":"36","author":"Lei","year":"2015","journal-title":"Hum. Mutat."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1038\/gim.2016.10","article-title":"Novel mutations in LRP6 highlight the role of WNT signaling in tooth agenesis","volume":"18","author":"Ockeloen","year":"2016","journal-title":"Genet. Med."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1007\/s00439-016-1733-z","article-title":"Tooth Agenesis and Orofacial Clefting: Genetic Brothers in Arms?","volume":"135","author":"Phan","year":"2016","journal-title":"Hum. Genet."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/s00439-015-1606-x","article-title":"Systematic analysis of copy number variants of a large cohort of orofacial cleft patients identifies candidate genes for orofacial clefts","volume":"135","author":"Conte","year":"2016","journal-title":"Hum. Genet."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1002\/bdra.20571","article-title":"Identification of Microdeletions in Candidate Genes for Cleft Lip and\/or Palate","volume":"85","author":"Shi","year":"2009","journal-title":"Birth Defects Res. A Clin. Mol. Teratol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1136\/jmg.2007.052191","article-title":"Identification of novel candidate genes associated with cleft lip and palate using array comparative genomic hybridisation","volume":"45","author":"Osoegawa","year":"2008","journal-title":"J. Med. Genet."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/5\/2051\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:48:02Z","timestamp":1760122082000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/5\/2051"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,4]]},"references-count":81,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["jcm12052051"],"URL":"https:\/\/doi.org\/10.3390\/jcm12052051","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,4]]}}}