{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T21:06:34Z","timestamp":1790024794018,"version":"4.0.1"},"reference-count":43,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,27]],"date-time":"2022-12-27T00:00:00Z","timestamp":1672099200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Health Systems Research Institute (HSRI) of Thailand","award":["64\u2013123"],"award-info":[{"award-number":["64\u2013123"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Objective: To investigate dental anomalies and the molecular etiology of a patient with Ellis\u2013van Creveld syndrome and two patients with Bardet\u2013Biedl syndrome, two examples of ciliopathies. Patients and Methods: Clinical examination, radiographic evaluation, whole exome sequencing, and Sanger direct sequencing were performed. Results: Patient 1 had Ellis\u2013van Creveld syndrome with delayed dental development or tooth agenesis, and multiple frenula, the feature found only in patients with mutations in ciliary genes. A novel homozygous mutation in EVC2 (c.703G&gt;C; p.Ala235Pro) was identified. Patient 2 had Bardet\u2013Biedl syndrome with a homozygous frameshift mutation (c.389_390delAC; p.Asn130ThrfsTer4) in BBS7. Patient 3 had Bardet\u2013Biedl syndrome and carried a heterozygous mutation (c.389_390delAC; p.Asn130ThrfsTer4) in BBS7 and a homozygous mutation in BBS2 (c.209G&gt;A; p.Ser70Asn). Her clinical findings included global developmental delay, disproportionate short stature, myopia, retinitis pigmentosa, obesity, pyometra with vaginal atresia, bilateral hydronephrosis with ureteropelvic junction obstruction, bilateral genu valgus, post-axial polydactyly feet, and small and thin fingernails and toenails, tooth agenesis, microdontia, taurodontism, and impaired dentin formation. Conclusions: EVC2, BBS2, and BBS7 mutations found in our patients were implicated in malformation syndromes with dental anomalies including tooth agenesis, microdontia, taurodontism, and impaired dentin formation.<\/jats:p>","DOI":"10.3390\/genes14010084","type":"journal-article","created":{"date-parts":[[2022,12,28]],"date-time":"2022-12-28T08:42:22Z","timestamp":1672216942000},"page":"84","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Dental Anomalies in Ciliopathies: Lessons from Patients with BBS2, BBS7, and EVC2 Mutations"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9841-0881","authenticated-orcid":false,"given":"Piranit","family":"Kantaputra","sequence":"first","affiliation":[{"name":"Division of Pediatric Dentistry, Department of Orthodontics and Pediatric Dentistry, Faculty of Dentistry, Chiang Mai University, Chiang Mai 50200, Thailand"},{"name":"Dentaland Clinic, Chiang Mai 50200, Thailand"},{"name":"Center of Excellence in Medical Genetics Research, Faculty of Dentistry, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prapai","family":"Dejkhamron","sequence":"additional","affiliation":[{"name":"Division of Pediatric Endocrinology, Department of Pediatrics, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rekwan","family":"Sittiwangkul","sequence":"additional","affiliation":[{"name":"Division of Pediatric Cardiology, Department of Pediatrics, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamornwan","family":"Katanyuwong","sequence":"additional","affiliation":[{"name":"Division of Pediatric Neurology, Department of Pediatrics, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chumpol","family":"Ngamphiw","sequence":"additional","affiliation":[{"name":"National Biobank of Thailand, National Science and Technology Development Agency, Pathum Thani 12120, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuntigar","family":"Sonsuwan","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Worrachet","family":"Intachai","sequence":"additional","affiliation":[{"name":"Center of Excellence in Medical Genetics Research, Faculty of Dentistry, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sissades","family":"Tongsima","sequence":"additional","affiliation":[{"name":"National Biobank of Thailand, National Science and Technology Development Agency, Pathum Thani 12120, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip L.","family":"Beales","sequence":"additional","affiliation":[{"name":"Genetics and Genomic Medicine Program, UCL Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Worakanya","family":"Buranaphatthana","sequence":"additional","affiliation":[{"name":"Department of Oral Biology and Diagnostic Sciences, Faculty of Dentistry, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1038\/nrm.2017.60","article-title":"Genes and molecular pathways underpinning ciliopathies","volume":"18","author":"Reiter","year":"2017","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"a027904","DOI":"10.1101\/cshperspect.a027904","article-title":"The Biology of Ciliary Dynamics","volume":"9","author":"Hsu","year":"2017","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1038\/nrg2774","article-title":"The primary cilium: A signalling centre during vertebrate development","volume":"11","author":"Goetz","year":"2010","journal-title":"Nat. Rev. Genet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"620","DOI":"10.4103\/0301-4738.194328","article-title":"Bardet-Biedl syndrome: Genetics, molecular pathophysiology, and disease management","volume":"64","author":"Priya","year":"2016","journal-title":"Indian J. Ophthalmol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/j.gde.2013.04.008","article-title":"Hedgehog signaling from the primary cilium to the nucleus: An emerging picture of ciliary localization, trafficking and transduction","volume":"23","author":"Nozawa","year":"2013","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1038\/nrm3085","article-title":"Ciliogenesis: Building the cell\u2019s antenna","volume":"12","author":"Ishikawa","year":"2011","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1186\/gm275","article-title":"A systems-biology approach to understanding the ciliopathy disorders","volume":"3","author":"Lee","year":"2011","journal-title":"Genome Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1111\/j.1600-0714.1996.tb00198.x","article-title":"Anomalies in the permanent dentition and other oral findings in 29 individuals with Laurence-Moon-Bardet-Biedl syndrome","volume":"25","author":"Riise","year":"1996","journal-title":"J. Oral. Pathol. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.3109\/00016357.2013.794389","article-title":"Taurodontism: A minor diagnostic criterion in Laurence-Moon\/Bardet-Biedl syndromes","volume":"71","author":"Andersson","year":"2013","journal-title":"Acta Odontol. Scand."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1038\/ejhg.2012.115","article-title":"Bardet-Biedl syndrome","volume":"21","author":"Forsythe","year":"2013","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1177\/0022034517713688","article-title":"Role of Primary Cilia in Odontogenesis","volume":"96","author":"Hampl","year":"2017","journal-title":"J. Dent. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1101\/gr.107524.110","article-title":"The Genome Analysis Toolkit: A MapReduce framework for analyzing next-generation DNA sequencing data","volume":"20","author":"McKenna","year":"2010","journal-title":"Genome Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1093\/bioinformatics\/btp324","article-title":"Fast and accurate short read alignment with Burrows-Wheeler transform","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1186\/s13059-016-0974-4","article-title":"The Ensembl Variant Effect Predictor","volume":"17","author":"McLaren","year":"2016","journal-title":"Genome Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2256","DOI":"10.1126\/science.1063525","article-title":"Triallelic inheritance in Bardet-Biedl syndrome, a Mendelian recessive disorder","volume":"293","author":"Katsanis","year":"2001","journal-title":"Science"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1016\/j.cell.2007.03.053","article-title":"A core complex of BBS proteins cooperates with the GTPase Rab8 to promote ciliary membrane biogenesis","volume":"129","author":"Nachury","year":"2007","journal-title":"Cell"},{"key":"ref_17","first-page":"2372","article-title":"BBS7 is required for BBSome formation and its absence in mice results in Bardet-Biedl syndrome phenotypes and selective abnormalities in membrane protein trafficking","volume":"126","author":"Zhang","year":"2013","journal-title":"J. Cell Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1038\/nrg910","article-title":"Beyond Mendel: An evolving view of human genetic disease transmission","volume":"3","author":"Badano","year":"2002","journal-title":"Nat. Rev. Genet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e53910","DOI":"10.7554\/eLife.53910","article-title":"Structure of the human BBSome core complex","volume":"9","author":"Klink","year":"2020","journal-title":"Elife"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1630","DOI":"10.1101\/gad.1194004","article-title":"Loss of C. elegans BBS-7 and BBS-8 protein function results in cilia defects and compromised intraflagellar transport","volume":"18","author":"Blacque","year":"2004","journal-title":"Genes Dev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1093\/hmg\/dds004","article-title":"BBS proteins interact genetically with the IFT pathway to influence SHH-related phenotypes","volume":"21","author":"Zhang","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"ref_22","unstructured":"Hennekam, R.C., Allanson, J.E., and Krantz, I.D. (2010). Gorlin\u2019s Syndromes of the Head and Neck, Oxford University Press."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1038\/ncb1670","article-title":"Kif3a constrains beta-catenin-dependent Wnt signalling through dual ciliary and non-ciliary mechanisms","volume":"10","author":"Corbit","year":"2008","journal-title":"Nat. Cell. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1016\/j.devcel.2015.07.016","article-title":"Components of Intraflagellar Transport Complex A Function Independently of the Cilium to Regulate Canonical Wnt Signaling in Drosophila","volume":"34","author":"Balmer","year":"2015","journal-title":"Dev. Cell"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1177\/0022034514528211","article-title":"Primary cilia integrate hedgehog and Wnt signaling during tooth development","volume":"93","author":"Liu","year":"2014","journal-title":"J. Dent. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1038\/ng.2007.12","article-title":"Disruption of the basal body compromises proteasomal function and perturbs intracellular Wnt response","volume":"39","author":"Gerdes","year":"2007","journal-title":"Nat. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1172\/JCI37041","article-title":"Mechanistic insights into Bardet-Biedl syndrome, a model ciliopathy","volume":"119","author":"Zaghloul","year":"2009","journal-title":"J. Clin. Investig."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1016\/j.devcel.2012.07.004","article-title":"A Smoothened-Evc2 complex transduces the Hedgehog signal at primary cilia","volume":"23","author":"Dorn","year":"2012","journal-title":"Dev. Cell"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Blair, H.J., Tompson, S., Liu, Y.N., Campbell, J., MacArthur, K., Ponting, C.P., Ruiz-Perez, V.L., and Goodship, J.A. (2011). Evc2 is a positive modulator of Hedgehog signalling that interacts with Evc at the cilia membrane and is also found in the nucleus. BMC Biol., 9.","DOI":"10.1186\/1741-7007-9-14"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.devcel.2014.01.021","article-title":"EFCAB7 and IQCE regulate hedgehog signaling by tethering the EVC-EVC2 complex to the base of primary cilia","volume":"28","author":"Pusapati","year":"2014","journal-title":"Dev. Cell"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1002\/dvg.22879","article-title":"Generation of Evc2\/Limbin global and conditional KO mice and its roles during mineralized tissue formation","volume":"53","author":"Zhang","year":"2015","journal-title":"Genesis"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2903","DOI":"10.1242\/dev.007542","article-title":"Evc is a positive mediator of Ihh-regulated bone growth that localises at the base of chondrocyte cilia","volume":"134","author":"Blair","year":"2007","journal-title":"Development"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1177\/0022034512471826","article-title":"Evc regulates a symmetrical response to Shh signaling in molar development","volume":"92","author":"Nakatomi","year":"2013","journal-title":"J. Dent. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1177\/0022034516683674","article-title":"Loss of Function of Evc2 in Dental Mesenchyme Leads to Hypomorphic Enamel","volume":"96","author":"Zhang","year":"2017","journal-title":"J. Dent. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2131","DOI":"10.1002\/ajmg.a.34125","article-title":"Two novel heterozygous mutations of EVC2 cause a mild phenotype of Ellis-van Creveld syndrome in a Chinese family","volume":"155","author":"Shen","year":"2011","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Pawlaczyk-Kamie\u0144ska, T., Winiarska, H., Kulczyk, T., and Cofta, S. (2020). Dental Anomalies in Rare, Genetic Ciliopathic Disorder-A Case Report and Review of Literature. Int. J. Environ. Res. Public Health, 17.","DOI":"10.3390\/ijerph17124337"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3797","DOI":"10.1093\/emboj\/16.13.3797","article-title":"Beta-catenin is a target for the ubiquitin-proteasome pathway","volume":"16","author":"Aberle","year":"1997","journal-title":"EMBO J."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1177\/0022034517741283","article-title":"Essential Role of IFT140 in Promoting Dentinogenesis","volume":"97","author":"Li","year":"2018","journal-title":"J. Dent. Res."},{"key":"ref_39","first-page":"3038","article-title":"MicroRNA-30a suppresses the proliferation, migration and invasion of human renal cell carcinoma cells by directly targeting ADAM9","volume":"16","author":"Jiang","year":"2018","journal-title":"Oncol. Lett."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1242\/dev.027979","article-title":"Primary cilia regulate Shh activity in the control of molar tooth number","volume":"136","author":"Ohazama","year":"2009","journal-title":"Development"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1007\/s00467-007-0435-0","article-title":"Bardet-Biedl syndrome: Beyond the cilium","volume":"22","author":"Tobin","year":"2007","journal-title":"Pediatr. Nephrol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/nature03818","article-title":"Functional coordination of intraflagellar transport motors","volume":"436","author":"Ou","year":"2005","journal-title":"Nature"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1126\/science.1139740","article-title":"Patched1 regulates hedgehog signaling at the primary cilium","volume":"317","author":"Rohatgi","year":"2007","journal-title":"Science"}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/14\/1\/84\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:52:59Z","timestamp":1760147579000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/14\/1\/84"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,27]]},"references-count":43,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,1]]}},"alternative-id":["genes14010084"],"URL":"https:\/\/doi.org\/10.3390\/genes14010084","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,27]]}}}