Primary failure of eruption and PTH1R: the importance of a genetic diagnosis for orthodontic treatment planning.
BACKGROUND
Primary failure of eruption (PFE) is characterized by nonsyndromic eruption failure of permanent teeth in the absence of mechanical obstruction. Recent studies support that this dental phenotype is inherited and that mutations in PTH1R genes explain several familial cases of PFE. The objective of our study was to investigate how genetic analysis can be used with clinical diagnostic information for improved orthodontic management of PFE.


METHODS
We evaluated a family (n = 12) that segregated an autosomal dominant form of PFE with 5 affected and 7 unaffected persons. Nine available family members (5 male, 4 female) were enrolled and subsequently characterized clinically and genetically.


RESULTS
In this family, PFE segregated with a novel mutation in the PTH1R gene. A heterozygous c.1353-1 G>A sequence alteration caused a putative splice-site mutation and skipping of exon 15 that segregated with the PFE phenotype in all affected family members.


CONCLUSIONS
A PTH1R mutation is strongly associated with failure of orthodontically assisted eruption or tooth movement and should therefore alert clinicians to treat PFE and ankylosed teeth with similar caution-ie, avoid orthodontic treatment with a continuous archwire.
Frazier-Bowers
Sylvia A
SA
Department of Orthodontics, University of North Carolina, Chapel Hill, NC, USA. sylvia_frazier@dentistry.unc.edu
Simmons
Darrin
D
Wright
J Timothy
JT
Proffit
William R
WR
Ackerman
James L
JL
D000293:Adolescent; D000328:Adult; D019229:Dentition, Permanent; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D050793:Orthodontic Extrusion; D009971:Orthodontics, Corrective / Q000379:methods; D010347:Patient Care Planning; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D044168:Receptor, Parathyroid Hormone, Type 1 / Q000235:genetics*; D020254:Tooth Ankylosis / Q000150:complications / Q000235:genetics / Q000628:therapy; D014076:Tooth Diseases / Q000150:complications / Q000235:genetics*; D014078:Tooth Eruption / Q000235:genetics*; D017211:Treatment Failure
C473449:PTH1R protein, human; D044168:Receptor, Parathyroid Hormone, Type 1