title: Mutations in WNT10A are present in more than half of isolated hypodontia cases.
abstract: BACKGROUND
  Dental agenesis is the most common, often heritable, developmental anomaly in humans. Mutations in MSX1, PAX9, AXIN2 and the ectodermal dysplasia genes EDA, EDAR and EDARADD have been detected in familial severe tooth agenesis. However, until recently, in the majority of cases (∼90%) the genetic factor could not be identified, implying that other genes must be involved. Recent insights into the role of Wnt10A in tooth development, and the finding of hypodontia in carriers of the autosomal recessive disorder, odontooncychodermal dysplasia, due to mutations in WNT10A (OMIM 257980; OODD), make WNT10A an interesting candidate gene for dental agenesis.
  
  
  METHODS
  In a panel of 34 patients with isolated hypodontia, the candidate gene WNT10A and the genes MSX1, PAX9, IRF6 and AXIN2 have been sequenced. The probands all had isolated agenesis of between six and 28 teeth.
  
  
  RESULTS
  WNT10A mutations were identified in 56% of the cases with non-syndromic hypodontia. MSX1, PAX9 and AXIN2 mutations were present in 3%, 9% and 3% of the cases, respectively.
  
  
  CONCLUSIONS
  The authors identified WNT10A as a major gene in the aetiology of isolated hypodontia. By including WNT10A in the DNA diagnostics of isolated tooth agenesis, the yield of molecular testing in this condition was significantly increased from 15% to 71%.
authors.affiliation: Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands. m.j.h.vandenboogaard@umcutrecht.nl
authors.forename: Marie-José
authors.initials: MJ
authors.lastname: van den Boogaard
authors.forename: Marijn
authors.initials: M
authors.lastname: Créton
authors.forename: Yvon
authors.initials: Y
authors.lastname: Bronkhorst
authors.forename: Annemieke
authors.initials: A
authors.lastname: van der Hout
authors.forename: Eric
authors.initials: E
authors.lastname: Hennekam
authors.forename: Dick
authors.initials: D
authors.lastname: Lindhout
authors.forename: Marco
authors.initials: M
authors.lastname: Cune
authors.forename: Hans Kristian
authors.initials: HK
authors.lastname: Ploos van Amstel
mesh_terms: D000293:Adolescent; D000328:Adult; D000848:Anodontia / Q000235:genetics*; D060466:Axin Protein / Q000235:genetics; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D051957:MSX1 Transcription Factor / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D051764:PAX9 Transcription Factor / Q000235:genetics; D010641:Phenotype; D051153:Wnt Proteins / Q000235:genetics*
chemical_list: C491761:AXIN2 protein, human; D060466:Axin Protein; D051957:MSX1 Transcription Factor; C484083:MSX1 protein, human; D051764:PAX9 Transcription Factor; C497323:PAX9 protein, human; C484142:WNT10A protein, human; D051153:Wnt Proteins