Primary failure of eruption (PFE)--clinical and molecular genetics analysis.
BACKGROUND
The term "primary failure of eruption" (PFE) refers to the complete or partial failure of a primary non-ankylosed tooth to erupt due to a disturbance of the eruption mechanism. Up to now, the molecular basis for this failure was unknown.


METHODS
Four families were studied in whom at least two members were affected by non-syndromic PFE as part of a clinical and molecular genetics study. Radiological diagnostics (OPTs) were carried out in all patients and their unaffected relatives (control group). The genetic analysis included a genomewide linkage analysis followed by direct DNA sequencing of positional candidate genes.


RESULTS
Starting from the index patients, we were able to reconstruct pedigrees over two and/or three generations in the families that indicated an autosomal-dominant mode of inheritance of non-syndromic PFE. Fifteen patients were diagnosed with PFE. Gender distribution was nearly equal (7 female, 8 male). Molecular genetic analysis of the PTHR1 gene revealed three distinct heterozygous mutations (c.1050-3C>G; c.543+1G>A; c.463G>T). Unaffected persons exhibited no mutations.


CONCLUSIONS
Knowledge of the genetic causes of non-syndromic PFE can now be used for the differential diagnosis of eruption failure. It permits affected family members to be identified early and may lead to new treatment possibilities in the long term. The genetically-verified diagnosis of "primary failure of eruption" can protect patients and orthodontists from years of futile treatment, because orthodontic treatment alone does not lead to success. Moreover, it has a negative influence on unaffected teeth and areas of the jaw.
Stellzig-Eisenhauer
Angelika
A
Department of Orthodontics, University of Würzburg, Würzburg, Germany. Stellzig_A@klinik.uni-wuerzburg.de
Decker
Eva
E
Meyer-Marcotty
Philipp
P
Rau
Christiane
C
Fiebig
Britta S
BS
Kress
Wolfram
W
Saar
Kathrin
K
Rüschendorf
Franz
F
Hubner
Norbert
N
Grimm
Tiemo
T
Witt
Emil
E
Weber
Bernhard H F
BH
D000293:Adolescent; D000328:Adult; D002648:Child; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008297:Male; D009154:Mutation; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011859:Radiography; D044168:Receptor, Parathyroid Hormone, Type 1 / Q000235:genetics*; D014078:Tooth Eruption / Q000235:genetics*; D014097:Tooth, Unerupted / Q000000981:diagnostic imaging* / Q000235:genetics*; D055815:Young Adult
C473449:PTH1R protein, human; D044168:Receptor, Parathyroid Hormone, Type 1