{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T04:37:07Z","timestamp":1782535027760,"version":"3.54.5"},"reference-count":38,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T00:00:00Z","timestamp":1738022400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea (NRF)","doi-asserted-by":"publisher","award":["RS-2023-NR076663"],"award-info":[{"award-number":["RS-2023-NR076663"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea (NRF)","doi-asserted-by":"publisher","award":["2022R1F1A1074271"],"award-info":[{"award-number":["2022R1F1A1074271"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background\/Objectives: Tooth agenesis (TA) is a developmental anomaly prevalent in humans. It is particularly significant in children and adolescents because it is related to esthetic, physiological, and functional problems, including malocclusion, periodontal damage, and insufficient alveolar growth. WNT10A mutations have been identified as the main genetic alterations associated with tooth agenesis. Most previous studies have investigated WNT10A mutations in patients with tooth agenesis using single nucleotide polymorphism (SNP) arrays or exome sequencing. In this study, we conducted a comprehensive profiling of mutations within the exons and introns of WNT10A in Korean patients with non-syndromic tooth agenesis. Methods: Saliva samples were collected from Korean children and adolescents with non-syndromic tooth agenesis. Tagmentation-based sequencing was conducted to acquire mutation information for all exonic and intronic bases of the WNT10A gene. Results: Mutations were detected exclusively in the patient samples: 629C&gt;G and 1100C&gt;T in exon 1, 1977T&gt;C in intron 1, 10256C&gt;T and 10382G&gt;A in exon 3, and 15953G&gt;A in intron 4. Additional mutations were also observed at high ratios in the patient samples. Conclusions: The mutations identified in this study differ from previous findings. These results may provide useful information for understanding the pathogenicity of WNT10A mutations in Korean patients with tooth agenesis and support future diagnostic and therapeutic approaches.<\/jats:p>","DOI":"10.3390\/diagnostics15030310","type":"journal-article","created":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T10:44:30Z","timestamp":1738061070000},"page":"310","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Exonic and Intronic WNT10A Variants Isolated from Korean Children with Non-Syndromic Tooth Agenesis"],"prefix":"10.3390","volume":"15","author":[{"given":"Yeonjin","family":"Ju","sequence":"first","affiliation":[{"name":"Department of Pediatric Dentistry, School of Dentistry, Dental and Life Science Institute, Pusan National University, Yangsan 50612, Republic of Korea"},{"name":"Department of Pediatric Dentistry, Dental Research Institute, Pusan National University Dental Hospital, Yangsan 50612, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joo Yeon","family":"Lee","sequence":"additional","affiliation":[{"name":"New Drug Development Center, OSONG Medical Innovation Foundation, Cheongju 28160, Republic of Korea"},{"name":"Department of Biomedical Science, Graduate School of Medicine, Hanyang University, Seoul 04763, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Woochang","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Pre-Medicine, College of Medicine, Hanyang University, Seoul 04763, Republic of Korea"},{"name":"Hanyang Institute of Bioscience and Biotechnology, Hanyang University, Seoul 04763, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9777-0196","authenticated-orcid":false,"given":"Jonghyun","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Pediatric Dentistry, School of Dentistry, Dental and Life Science Institute, Pusan National University, Yangsan 50612, Republic of Korea"},{"name":"Department of Pediatric Dentistry, Dental Research Institute, Pusan National University Dental Hospital, Yangsan 50612, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7588-7393","authenticated-orcid":false,"given":"Hyung-Sik","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Oral Biochemistry, School of Dentistry, Pusan National University, Yangsan 50612, Republic of Korea"},{"name":"Dental and Life Science Institute, Pusan National University, Yangsan 50612, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junho K.","family":"Hur","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, Graduate School of Medicine, Hanyang University, Seoul 04763, Republic of Korea"},{"name":"Hanyang Institute of Bioscience and Biotechnology, Hanyang University, Seoul 04763, Republic of Korea"},{"name":"Department of Genetics, College of Medicine, Hanyang University, Seoul 04763, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eungyung","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pediatric Dentistry, School of Dentistry, Dental and Life Science Institute, Pusan National University, Yangsan 50612, Republic of Korea"},{"name":"Department of Pediatric Dentistry, Dental Research Institute, Pusan National University Dental Hospital, Yangsan 50612, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Al-Ani, A.H., Antoun, J.S., Thomson, W.M., Merriman, T.R., and Farella, M. (2017). Hypodontia: An Update on Its Etiology, Classification, and Clinical Management. BioMed Res. Int., 2017.","DOI":"10.1155\/2017\/9378325"},{"key":"ref_2","first-page":"133","article-title":"Distribution of missing teeth and tooth morphology in patients with oligodontia","volume":"59","author":"Steen","year":"1992","journal-title":"ASDC J. Dent. Child."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1007\/s00056-016-0056-y","article-title":"Nonsyndromic oligodontia: Does the Tooth Agenesis Code (TAC) enable prediction of the causative mutation?","volume":"78","author":"Bock","year":"2017","journal-title":"J. Orofac. Orthop."},{"key":"ref_4","unstructured":"Letra, A., Chiquet, B., Hansen-Kiss, E., Menezes, S., Hunter, E., Adam, M.P., Ardinger, H.H., Pagon, R.A., Wallace, S.E., and Bean, L.J.H. (1993). Nonsyndromic Tooth Agenesis Overview, GeneReviews."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"355","DOI":"10.4041\/kjod.2021.51.5.355","article-title":"Prevalence and patterns of tooth agenesis among patients aged 12\u201322 years: A retrospective study","volume":"51","author":"Cafer","year":"2021","journal-title":"Korean J. Ortho"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1002\/wdev.66","article-title":"Diseases of the tooth: The genetic and molecular basis of inherited anomalies affecting the dentition","volume":"2","author":"Cobourne","year":"2013","journal-title":"WIREs Dev. Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.ajodo.2004.09.024","article-title":"A survey of hypodontia in Japanese orthodontic patients","volume":"129","author":"Endo","year":"2006","journal-title":"Am. J. Orthod. Dentofac. Orthop."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1111\/j.1601-0825.2007.01434.x","article-title":"The pattern and prevalence of hypodontia in Koreans","volume":"14","author":"Chung","year":"2008","journal-title":"Oral. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/j.ajodo.2006.05.025","article-title":"Congenitally missing mandibular second premolars: Clinical options","volume":"130","author":"Kokich","year":"2006","journal-title":"Am. J. Orthod. Dentofac. Orthop."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Letra, A., Fakhouri, W., Fonseca, R.F., Menezes, R., Kempa, I., Prasad, J.L., McHenry, T.G., Lidral, A.C., Moreno, L., and Murray, J.C. (2012). Interaction between IRF6 and TGFA Genes Contribute to the Risk of Nonsyndromic Cleft Lip\/Palate. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0045441"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.1177\/0022034518777460","article-title":"Patterns of Dental Agenesis Highlight the Nature of the Causative Mutated Genes","volume":"97","author":"Fournier","year":"2018","journal-title":"J. Dent. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1111\/odi.12931","article-title":"Genetic analysis: Wnt and other pathways in nonsyndromic tooth agenesis","volume":"25","author":"Yu","year":"2019","journal-title":"Oral. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1007\/s00056-021-00284-4","article-title":"Targeted next-generation sequencing (NGS) analysis of mutations in nonsyndromic tooth agenesis candidate genes","volume":"83","author":"Keskin","year":"2022","journal-title":"J. Orofac. Orthop."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1002\/ajmg.a.36243","article-title":"WNT10A mutations account for \u00bc of population-based isolated oligodontia and show phenotypic correlations","volume":"164","author":"Arzoo","year":"2014","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_15","unstructured":"Hongyu, Z., Xuanting, K., Jiabao, R., Shuo, Y., Chunyan, L., Yan, H., Ye, L., Lingqiang, M., Guozhong, Z., and Qingqing, D. (2021). A novel EDAR missense mutation identified by whole-exome sequencing with non-syndromic tooth agenesis in a Chinese family. Mol. Genet. Genom. Med., 9."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Adachi, J., Aoki, Y., Tatematsu, T., Goto, H., Nakayama, A., Nishiyama, T., Takahashi, K., Sana, M., Ota, A., and Machida, J. (2021). Novel MSX1 frameshift mutation in a Japanese family with nonsyndromic oligodontia. Hum. Genome Var., 8.","DOI":"10.1038\/s41439-021-00161-x"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"145","DOI":"10.2147\/TACG.S183212","article-title":"The role of PAX9 promoter gene polymorphisms in causing hypodontia: A study in the Jordanian population","volume":"11","author":"Khabour","year":"2018","journal-title":"Appl. Clin. Genet."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1007\/s10038-005-0353-6","article-title":"Axis inhibition protein 2 (AXIN2) polymorphisms may be a risk factor for selective tooth agenesis","volume":"51","author":"Mostowska","year":"2006","journal-title":"J. Hum. Genet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1002\/jez.b.21280","article-title":"The importance of signal pathway modulation in all aspects of tooth development","volume":"312B","author":"Tummers","year":"2009","journal-title":"J. Exp. Zool. Part. B: Mol. Dev. Evol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"133","DOI":"10.4041\/kjod.2008.38.2.133","article-title":"Characteristics of MSX1 gene in Korean nonsyndromic cleft lip and palate individuals","volume":"38","author":"Lee","year":"2008","journal-title":"Korean J. Ortho"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3168","DOI":"10.1111\/odi.14459","article-title":"MSX1 involved selective tooth agenesis and abnormal labial frenum, pedigree, and retrospective study","volume":"29","author":"Zhu","year":"2023","journal-title":"Oral. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.archoralbio.2008.08.002","article-title":"Axis inhibition protein 2 (AXIN2) polymorphisms and tooth agenesis","volume":"54","author":"Callahan","year":"2009","journal-title":"Arch. Oral. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Yanzi, G., Xiaohui, J., Zhi, W., Hu, L., and Wenli, L. (2023). The EDA\/EDAR\/NF-\u03baB pathway in non-syndromic tooth agenesis: A genetic perspective. Front. Genet., 14.","DOI":"10.3389\/fgene.2023.1168538"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Zhao, Z., Zhang, T., Li, T., Ye, Y., Feng, C., Wang, H., and Zhang, X. (2023). A novel EDAR variant identified in non-syndromic tooth agenesis: Insights from molecular dynamics. Arch. Oral. Biol., 146.","DOI":"10.1016\/j.archoralbio.2022.105600"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1007\/s00439-013-1360-x","article-title":"WNT10A variants are associated with non-syndromic tooth agenesis in the general population","volume":"133","author":"Song","year":"2014","journal-title":"Hum. Genet."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1136\/jmedgenet-2012-100750","article-title":"Mutations in WNT10A are present in more than half of isolated hypodontia cases","volume":"49","author":"Bronkhorst","year":"2012","journal-title":"J. Med. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.ajhg.2009.06.001","article-title":"WNT10A Mutations Are a Frequent Cause of a Broad Spectrum of Ectodermal Dysplasias with Sex-Biased Manifestation Pattern in Heterozygotes","volume":"85","author":"Bohring","year":"2009","journal-title":"Am. J. Hum. Genet."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1111\/j.1600-0722.2006.00340.x","article-title":"A numeric code for identifying patterns of human tooth agenesis: A new approach","volume":"114","author":"Tan","year":"2006","journal-title":"Eur. J. Oral. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1007\/s00056-013-0138-z","article-title":"Genetic background of nonsyndromic oligodontia: A systematic review and meta-analysis","volume":"74","author":"Ruf","year":"2013","journal-title":"J. Orofac. Orthop."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Kim, Y.H. (2011). Investigation of hypodontia as clinically related dental anomaly: Prevalence and characteristics. ISRN Dent., 2011.","DOI":"10.5402\/2011\/246135"},{"key":"ref_31","first-page":"160","article-title":"Taurodontism, variations in tooth number, and misshapened crowns in Wnt10a null mice and human kindreds","volume":"3","author":"Yang","year":"2015","journal-title":"Mol. Genet. Genom. Med."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Chu, K.Y., Wang, Y.L., Chen, J.T., Wang, Y.P., Wang, S.K., Chou, Y.R., Simmer, J.P., and Hu, J.C.C. (2021). Synergistic mutations of LRP6 and WNT10A in familial tooth agenesis. J. Pers. Med., 11.","DOI":"10.3390\/jpm11111217"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.archoralbio.2019.05.007","article-title":"WNT10A mutations causing oligodontia","volume":"103","author":"Park","year":"2019","journal-title":"Arch. Oral. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1111\/odi.13316","article-title":"Novel TSPEAR mutations in non-syndromic oligodontia","volume":"26","author":"Song","year":"2020","journal-title":"Oral. Dis."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Lalrinmawii, C., and Muppalaneni, N.B. (2023, January 6\u20138). An Overview of the Workflow of Next-Generation Sequencing Data Analysis. Proceedings of the 2023 4th International Conference on Electronics and Sustainable Communication Systems (ICESC), Coimbatore, India.","DOI":"10.1109\/ICESC57686.2023.10193007"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/nature24286","article-title":"DNA sequencing at 40: Past, present and future","volume":"550","author":"Shendure","year":"2017","journal-title":"Nature"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1007\/s00439-017-1809-4","article-title":"Deep intronic mutations and human disease","volume":"136","year":"2017","journal-title":"Hum. Genet."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Kurosawa, R., Iida, K., Ajiro, M., Awaya, T., Yamada, M., Kosaki, K., and Hagiwara, M. (2023). PDIVAS: Pathogenicity predictor for Deep-Intronic Variants causing Aberrant Splicing. BMC Genom., 24.","DOI":"10.1186\/s12864-023-09645-2"}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/15\/3\/310\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T10:37:55Z","timestamp":1759919875000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/15\/3\/310"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,28]]},"references-count":38,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["diagnostics15030310"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics15030310","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,28]]}}}