J Med Genet 49:327-331 doi:10.1136/jmedgenet-2012-100750
  • Developmental defects
  • Original article

Mutations in WNT10A are present in more than half of isolated hypodontia cases

  1. Hans Kristian Ploos van Amstel1
  1. 1Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands
  2. 2Department of Oral and Maxillofacial Surgery, Prosthodontics and Special Dental Care, University Medical Centre Utrecht, Utrecht, The Netherlands
  3. 3Department of Genetics, University Medical Center Groningen, The University of Groningen, Groningen, The Netherlands
  4. 4Department of Fixed and Removable Prosthodontics, Academic Centre for Dentistry and Oral Health, University Medical Center Groningen, The University of Groningen, Groningen, The Netherlands
  5. 5Department of Oral and Maxillofacial Surgery, Prosthodontics and Special Dental Care, St. Antonius Hospital Nieuwegein, Nieuwegein, The Netherlands
  1. Correspondence to Dr Marie-Jose van den Boogaard, University Medical Centre Utrecht, PO Box 85090, Utrecht 3508 AB, The Netherlands; m.j.h.vandenboogaard{at}
  1. Contributors M-JHvdB, Marijn C, Marco C and JPvA contributed to the conception and design of the study. M-JHvdB, Marijn C, YB, AvdH, Marco C and FAMH collected data. Marijn C and Marco C contributed to the referral of patients. YB and AvdH performed the molecular analysis. M-JvdB analysed the data and along with all the authors was involved in data interpretation. MJHvdB, Marco C and JPvA drafted the article. Marijn C, AvdH, DL, Marco C and JPvA critically revised the article for intellectual content. All the authors contributed to the final approval of the version to be submitted.

  • Received 6 January 2012
  • Revised 9 March 2012
  • Accepted 19 March 2012


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.

Conclusion 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%.


  • Funding This study is in part funded by the Dutch Association for Prosthetic Dentistry and Orofacial Pain (NVGPT).

  • Competing interests None.

  • Patient consent Patients gave their informed consent. The data are the results of daily clinical practice.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement The authors have additional clinical and dental data on the patients without a WNT10A mutation and the patients with a MSX1 and PAX9 mutation available in three additional tables.