{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:52:15Z","timestamp":1760147535106,"version":"build-2065373602"},"reference-count":37,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,2,10]],"date-time":"2023-02-10T00:00:00Z","timestamp":1675987200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Carlos III Health Institute (ISCIII)","award":["PI14\/01259","PI17\/00796 y","PI21\/01082"],"award-info":[{"award-number":["PI14\/01259","PI17\/00796 y","PI21\/01082"]}]},{"name":"European Regional Development Fund (ERDF)","award":["PI14\/01259","PI17\/00796 y","PI21\/01082"],"award-info":[{"award-number":["PI14\/01259","PI17\/00796 y","PI21\/01082"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>Ectodermal dysplasias (EDs) represent a heterogeneous group of genetic disorders characterized by the abnormal development of ectodermal-derived tissues. They include the involvement of the hair, nails, skin, sweat glands, and teeth. Pathogenic variants in EDA1 (Xq12\u201313.1; OMIM*300451), EDAR (2q11-q13; OMIM*604095), EDARADD (1q42-q43, OMIM*606603), and WNT10A (2q35; OMIM*606268) genes are responsible for most EDs. Bi-allelic pathogenic variants of WNT10A have been associated with autosomal recessive forms of ED, as well as non-syndromic tooth agenesis (NSTA). The potential phenotypic impact of associated modifier mutations in other ectodysplasin pathway genes has also been pointed out. We present on an 11-year-old Chinese boy with oligodontia, with conical-shaped teeth as the main phenotype, and other very mild ED signs. The genetic study identified the pathogenic variants WNT10A (NM_025216.3): c.310C &gt; T; p. (Arg104Cys) and c.742C &gt; T; p. (Arg248Ter) in compound heterozygosis, confirmed by parental segregation. In addition, the patient had the polymorphism EDAR (NM_022336.4): c.1109T &gt; C, p. (Val370Ala) in homozygosis, named EDAR370. A prominent dental phenotype with minor ectodermal symptoms is very suggestive of WNT10A mutations. In this case, the EDAR370A allele might also attenuate the severity of other ED signs.<\/jats:p>","DOI":"10.3390\/children10020356","type":"journal-article","created":{"date-parts":[[2023,2,13]],"date-time":"2023-02-13T03:28:46Z","timestamp":1676258926000},"page":"356","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Dental Phenotype with Minor Ectodermal Symptoms Suggestive of WNT10A Deficiency"],"prefix":"10.3390","volume":"10","author":[{"given":"Victoria-Eugenia","family":"Garc\u00eda-Mart\u00ednez","sequence":"first","affiliation":[{"name":"Alaquas Health Center, Departament General University Hospital, 46070 Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8566-0339","authenticated-orcid":false,"given":"Ximo","family":"Galiana-Vall\u00e9s","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Genetics, Clinical Analysis Service, Consortium General University Hospital, 46014 Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Otilia","family":"Zome\u00f1o-Alcal\u00e1","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Genetics, Clinical Analysis Service, Consortium General University Hospital, 46014 Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5865-5382","authenticated-orcid":false,"given":"Raquel","family":"Rodr\u00edguez-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Genetics, Clinical Analysis Service, Consortium General University Hospital, 46014 Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3942-2820","authenticated-orcid":false,"given":"Carmen","family":"Llena","sequence":"additional","affiliation":[{"name":"Primary Care Dentistry, Departament General University Hospital, 46070 Valencia, Spain"},{"name":"Departament of Stomatology, Universitat de Valencia, 46010 Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda del Carmen","family":"Mart\u00ednez-Romero","sequence":"additional","affiliation":[{"name":"Molecular Genetics Section, Biochemistry and Clinical Genetics Center, University Clinical Hospital Virgen de la Arrixaca, Health Sciences PhD Program-UCAM, 30109 Murcia, Spain"},{"name":"IMIB-Pascual Parrilla, 30007 Murcia, Spain"},{"name":"CIBERER-ISCIII, 28029 Madrid, Spain"},{"name":"Faculty of Medicine and Health Sciences, UCAM Catholic University of Murcia, 30109 Murcia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Encarna","family":"Guill\u00e9n-Navarro","sequence":"additional","affiliation":[{"name":"IMIB-Pascual Parrilla, 30007 Murcia, Spain"},{"name":"CIBERER-ISCIII, 28029 Madrid, Spain"},{"name":"Medical Genetics Section, Pediatrics Department, University Clinical Hospital Virgen de la Arrixaca, University of Murcia (UMU), 30120 Murcia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.yexcr.2013.08.002","article-title":"Signaling pathways regulating ectodermal cell fate choices","volume":"321","author":"Patthey","year":"2014","journal-title":"Exp. Cell Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.yexcr.2014.02.003","article-title":"Tooth, hair and claw: Comparing epithelial stem cell niches of ectodermal appendages","volume":"325","author":"Naveau","year":"2014","journal-title":"Exp. Cell Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1002\/ajmg.a.61045","article-title":"Ectodermal dysplasiasClassification and organization by phenotype, genotype and molecular pathway","volume":"179","author":"Wright","year":"2019","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1002\/humu.21384","article-title":"Only four genes (EDA1, EDAR, EDARADD and WNTA10A) account for 90% of hypohidrotic\/anhidrotic ectodermal dysplasia cases","volume":"32","author":"Cluzeau","year":"2011","journal-title":"Hum. Mutat."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2472","DOI":"10.1002\/ajmg.a.36550","article-title":"Etiology and pathogenesis of ectodermal dysplasias","volume":"164","author":"Itin","year":"2014","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1038\/ng0895-409","article-title":"X-linked anhidrotic (hypohidrotic) ectodermal dysplasia is caused by mutation in a novel transmembrane protein","volume":"13","author":"Kere","year":"1996","journal-title":"Nat. Genet."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1038\/414913a","article-title":"Gene defect in ectodermal dysplasia implicates a death domain adapter in development","volume":"414","author":"Headon","year":"2001","journal-title":"Nature"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1002\/humu.20295","article-title":"Mutations in EDAR account for one-quarter of non-ED1-related hypohidrotic ectodermal dysplasia","volume":"27","author":"Chassaing","year":"2006","journal-title":"Hum. Mutat."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1002\/ajmg.1320530207","article-title":"Ectodermal dysplasias: A clinical classification and a causal review","volume":"53","author":"Pinheiro","year":"1994","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1034\/j.1399-0004.2000.580601.x","article-title":"Ectodermal dysplasias: Not only \u00abskin\u00bb deep","volume":"58","author":"Priolo","year":"2000","journal-title":"Clin. Genet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1046\/j.1365-2230.2003.01319.x","article-title":"Towards a new classification of ectodermal dysplasia","volume":"28","author":"Lamartine","year":"2003","journal-title":"Clin. Exp. Dermatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1970","DOI":"10.1002\/ajmg.a.32852","article-title":"Towards a unified classification of the ectodermal dysplasias: Opportunities outweigh challenges","volume":"149","author":"Irvine","year":"2009","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_13","first-page":"2068","article-title":"Approach towards a new classification for ectodermal dysplasias: Integration of the clinical and molecular knowledge","volume":"149","author":"Priolo","year":"2009","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2273","DOI":"10.1007\/s00784-016-2020-z","article-title":"Permanent tooth agenesis in non-syndromic Robin sequence and cleft palate: Prevalence and patterns","volume":"21","author":"Hermus","year":"2017","journal-title":"Clin. Oral Investig."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"D1207","DOI":"10.1093\/nar\/gkaa1043","article-title":"The Human Phenotype Ontology in 2021","volume":"49","author":"Gargano","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_16","unstructured":"(2022, October 25). rs3827760 (SNP)\u2014Citations\u2014Homo_Sapiens\u2014Ensembl Genome Browser 108 [Internet]. Ensembl.org. Available online: https:\/\/oct2022.archive.ensembl.org\/Homo_sapiens\/Variation\/Citations?db=core;r=2:108896645-108897645;v=rs3827760;vdb=variation;vf=183839455."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.jdsr.2017.08.001","article-title":"A review on non-syndromic tooth agenesis associated with PAX9 mutations","volume":"54","author":"Fauzi","year":"2018","journal-title":"Jpn. Dent. Sci. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1111\/bjd.20601","article-title":"WNT I0 A, dermatology and dentistry","volume":"185","author":"Doolan","year":"2021","journal-title":"Brit. J. Dermatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"21","DOI":"10.3389\/fgene.2020.00021","article-title":"Pathogenic EDA Mutations in Chinese Han Families With Hypohidrotic Ectodermal Dysplasia and Genotype-Phenotype: A Correlation Analysis","volume":"11","author":"Han","year":"2020","journal-title":"Front. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1111\/1346-8138.14983","article-title":"Functional studies for a dominant mutation in the EDAR gene responsible for hypohidrotic ectodermal dysplasia","volume":"46","author":"Okita","year":"2019","journal-title":"J. Dermatol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1111\/j.1365-2133.2010.09670.x","article-title":"Mutations in EDARADD account for a small proportion of hypohidrotic ectodermal dysplasia cases","volume":"162","author":"Chassaing","year":"2010","journal-title":"Brit. J. Dermatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1007\/s00439-016-1741-z","article-title":"KDF1, encoding keratinocyte differentiation factor 1, is mutated in a multigenerational family with ectodermal dysplasia","volume":"136","author":"Shamseldin","year":"2017","journal-title":"Hum. Genet."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1111\/bjd.18007","article-title":"A novel de novo mutation substantiates KDF1 as a gene causing ectodermal dysplasia","volume":"18","author":"Manaspon","year":"2019","journal-title":"Br. J. Dermatol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1002\/mgg3.111","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. Genomic. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1186\/s13023-019-1251-x","article-title":"EDA, EDAR, EDARADD and WNT10A allelic variants in patients with ectodermal derivative impairment in the Spanish population","volume":"14","year":"2019","journal-title":"Orphanet. J. Rare Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1111\/bjd.13158","article-title":"Clinical features and WNT10A mutations in seven unrelated cases of Schopf-Schulz-Passarge syndrome","volume":"171","author":"Tziotzios","year":"2014","journal-title":"Br. J. Dermatol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1111\/cup.13743","article-title":"Eccrine Syringofibroadenoma as a clue for the diagnosis of Schopf-Schulz-Passarge syndrome in acquired palmoplantar keratoderma","volume":"47","author":"Alos","year":"2020","journal-title":"J. Cutan. Pathol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2455","DOI":"10.1002\/ajmg.a.36520","article-title":"The WNT10A gene in ectodermal dysplasias and selective tooth agenesis","volume":"164","author":"Mues","year":"2014","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2415","DOI":"10.1002\/ajmg.a.36616","article-title":"Update on ectodermal dysplasia clinical classification","volume":"164","author":"Pagnan","year":"2014","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1159\/000499325","article-title":"Turkish Ectodermal Dysplasia Cohort: From Phenotype to Genotype in 17 Families","volume":"157","author":"Bal","year":"2019","journal-title":"Cytogenet. Genome Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1111\/1346-8138.14201","article-title":"Case report of Schopf-Schulz-Passarge syndrome resulting from a missense mutation, p.Arg104Cys, in WNT10A","volume":"45","author":"Hsu","year":"2018","journal-title":"J. Dermatol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Zeng, B., Zhao, Q., Li, S., Lu, H., Lu, J., Ma, L., Zhao, W., and Yu, D. (2017). Novel EDA or EDAR Mutations Identified in Patients with X-Linked Hypohidrotic Ectodermal Dysplasia or Non-Syndromic Tooth Agenesis. Genes, 8.","DOI":"10.3390\/genes8100259"},{"key":"ref_33","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_34","first-page":"113","article-title":"Schopf-Schulz-Passarge Syndrome: Previously Unreported WNT10A Genotype and Phenotypes in 9 Family Members","volume":"99","author":"Zimmermann","year":"2019","journal-title":"Acta Derm.-Venereol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Capalbo, A., Alonso Valero, R., Jimenez-Almazan, J., Mir Pardo, P., Fabiani, M., Jim\u00e9nez, D., Simon, C., and Martin-Rodriguez, J. (2019). Optimizing clinical exome design and parallel gene-testing for recessive genetic conditions in preconception carrier screening: Translational research genomic data from 14,125 exomes. PLoS Genet., 15.","DOI":"10.1371\/journal.pgen.1008409"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1111\/j.1365-2133.2011.10620.x","article-title":"The EDAR370A allele attenuates the severity of hypohidrotic ectodermal dysplasia caused by EDA gene mutation","volume":"166","author":"Cluzeau","year":"2012","journal-title":"Br. J. Dermatol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Chang, S.H., Jobling, S., Brennan, K., and Headon, D.J. (2009). Enhanced Edar signalling has pleiotropic effects on craniofacial and cutaneous glands. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0007591"}],"container-title":["Children"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2227-9067\/10\/2\/356\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:31:02Z","timestamp":1760121062000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2227-9067\/10\/2\/356"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,10]]},"references-count":37,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["children10020356"],"URL":"https:\/\/doi.org\/10.3390\/children10020356","relation":{},"ISSN":["2227-9067"],"issn-type":[{"type":"electronic","value":"2227-9067"}],"subject":[],"published":{"date-parts":[[2023,2,10]]}}}