Identification of six novel PTH1R mutations in families with a history of primary failure of tooth eruption

PLoS One. 2013 Sep 18;8(9):e74601. doi: 10.1371/journal.pone.0074601. eCollection 2013.


Primary Failure of tooth Eruption (PFE) is a non-syndromic disorder which can be caused by mutations in the parathyroid hormone receptor 1 gene (PTH1R). Traditionally, the disorder has been identified clinically based on post-emergent failure of eruption of permanent molars. However, patients with PTH1R mutations will not benefit from surgical and/or orthodontic treatment and it is therefore clinically important to establish whether a given failure of tooth eruption is caused by a PTH1R defect or not. We analyzed the PTH1R gene in six patients clinically diagnosed with PFE, all of which had undergone surgical and/or orthodontic interventions, and identified novel PTH1R mutations in all. Four of the six mutations were predicted to abolish correct mRNA maturation either through introduction of premature stop codons (c.947C>A and c.1082G>A), or by altering correct mRNA splicing (c.544-26_544-23del and c.989G>T). The latter was validated by transfection of minigenes. The six novel mutations expand the mutation spectrum for PFE from eight to 14 pathogenic mutations. Loss-of-function mutations in PTH1R are also associated with recessively inherited Blomstrand chondrodysplasia. We compiled all published PTH1R mutations and identified a mutational overlap between Blomstrand chondrodysplasia and PFE. The results suggest that a genetic approach to preclinical diagnosis will have important implication for surgical and orthodontic treatment of patients with failure of tooth eruption.

MeSH terms

  • Adolescent
  • Adult
  • Base Sequence
  • Child
  • DNA Mutational Analysis
  • Exostoses, Multiple Hereditary / genetics
  • Family
  • Female
  • Humans
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Mutation / genetics*
  • Osteochondrodysplasias / genetics
  • Pedigree
  • Radiography, Panoramic
  • Receptor, Parathyroid Hormone, Type 1 / genetics*
  • Tooth Diseases / diagnostic imaging
  • Tooth Diseases / genetics*
  • Young Adult


  • PTH1R protein, human
  • Receptor, Parathyroid Hormone, Type 1

Supplementary concepts

  • Chondrodysplasia, blomstrand type
  • Failure of Tooth Eruption, Primary

Grants and funding

The authors have no support or funding to report.