title: Expanding the spectrum of PTH1R mutations in patients with primary failure of tooth eruption.
abstract: OBJECTIVE
  Primary failure of tooth eruption (PFE) is a rare autosomal-dominant disease characterized by severe lateral open bite as a consequence of incomplete eruption of posterior teeth. Heterozygous mutations in the parathyroid hormone 1 receptor (PTH1R) gene have been shown to cause PFE likely due to protein haploinsufficiency. To further expand on the mutational spectrum of PFE-associated mutations, we report here on the sequencing results of the PTH1R gene in 70 index PFE cases.
  
  
  METHODS
  Sanger sequencing of the PTH1R coding exons and their immediate flanking intronic sequences was performed with DNA samples from 70 index PFE cases.
  
  
  RESULTS
  We identified a total of 30 unique variants, of which 12 were classified as pathogenic based on their deleterious consequences on PTH1R protein while 16 changes were characterized as unclassified variants with as yet unknown effects on disease pathology. The remaining two variants represent common polymorphisms.
  
  
  CONCLUSIONS
  Our data significantly increase the number of presently known unique PFE-causing PTH1R mutations and provide a series of variants with unclear pathogenicity which will require further in vitro assaying to determine their effects on protein structure and function.
  
  
  CONCLUSIONS
  Management of PTH1R-associated PFE is problematic, in particular when teeth are exposed to orthodontic force. Therefore, upon clinical suspicion of PFE, molecular DNA testing is indicated to support decision making for further treatment options.
authors.affiliation: Institute of Human Genetics, University of Regensburg, Franz-Josef-Strauss-Allee 11, 93053, Regensburg, Germany.
authors.forename: Helmut
authors.initials: H
authors.lastname: Roth
authors.forename: Lars G
authors.initials: LG
authors.lastname: Fritsche
authors.forename: Christoph
authors.initials: C
authors.lastname: Meier
authors.forename: Peter
authors.initials: P
authors.lastname: Pilz
authors.forename: Martin
authors.initials: M
authors.lastname: Eigenthaler
authors.forename: Philipp
authors.initials: P
authors.lastname: Meyer-Marcotty
authors.forename: Angelika
authors.initials: A
authors.lastname: Stellzig-Eisenhauer
authors.forename: Peter
authors.initials: P
authors.lastname: Proff
authors.forename: Cláudia M
authors.initials: CM
authors.lastname: Kanno
authors.forename: Bernhard Hf
authors.initials: BH
authors.lastname: Weber
mesh_terms: D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D044168:Receptor, Parathyroid Hormone, Type 1 / Q000235:genetics*; D014078:Tooth Eruption / Q000235:genetics*
chemical_list: C473449:PTH1R protein, human; D044168:Receptor, Parathyroid Hormone, Type 1