Abstract
Objectives
The goal of this work was to identify all known gene mutations that have been associated with the development of nonsyndromic oligodontia.
Methods
A systematic literature search was performed electronically in two databases (PubMed, Medpilot) supplemented by a hand search. Articles published up to March 2012 were considered. Search terms were combined as follows: oligodontia and genes, oligodontia and mutations, tooth agenesis and genes, and tooth agenesis and mutations. A meta-analysis of the data was conducted based on the Tooth Agenesis Code (TAC).
Results
Seven genes are currently known to have a potential for causing nonsyndromic oligodontia. All these genes vary both in terms of number of identified mutations and in terms of number of documented patients: 33 mutations and 93 patients are on record for PAX9, 10 mutations and 51 patients for EDA, 12 mutations and 33 patients for MSX1, 6 mutations and 17 patients for AXIN2, and 1 mutation in 1 patient for EDARADD, NEMO, and KRT17 each. A total TAC score of 250 was found to have cutoff properties, as 100% of MSX1 and 80% of EDA patients exhibited TAC ≤250, whereas 96.9% of PAX9 and 90% of AXIN2 patients exhibited TAC >250. Furthermore, 94.3% of EDA patients but only 28.6% of MSX1 patients exhibited odd-numbered TAC scores in at least one quadrant, and 72.7% of PAX9 but none of the AXIN2 patients were found to show TAC scores of 112 in at least one quadrant.
Conclusion
In order of decreasing frequency, PAX9, EDA, MSX1, AXIN2, EDARADD, NEMO, and KRT17 are the seven genes currently known to have a potential for causing nonsyndromic oligodontia. TAC scores enabled us to identify an association between oligodontia phenotypes and genotypes in the patients covered by this meta-analysis.
Zusammenfassung
Fragestellung
Identifizierung aller bekannten Genmutationen, die mit der Entstehung nonsyndromaler Oligodontien assoziiert werden.
Methodik
Eine systematische elektronische Literatursuche bis einschließlich März 2012 wurde in zwei Datenbanken (PubMed, Medpilot) durchgeführt und durch eine Handsuche ergänzt. Folgende Suchbegriff-Kombinationen wurden verwendet: oligodontia and genes , oligodontia and mutations , tooth agenesis and genes , tooth agenesis and mutations. Auf der Grundlage des Tooth Agenesis Codes (TAC) wurde eine Metasnalyse der Daten durchgeführt.
Ergebnisse
Zwischen den sieben bisher bekannten Genen, die nonsyndromale Oligodontien verursachen können, variiert sowohl die Anzahl der identifizierten Mutationen (M) je Gen als auch die Anzahl der in der Literatur beschriebenen Patienten (P): PAX9 (33 M, 93 P), EDA (10M, 51P), MSX1 (12M, 33P), AXIN2 (6M, 17P), EDARADD, NEMO und KRT17 (je 1M/1P). Der TAC-Summenwert 250 besaß Trennwerteigenschaften: TAC ≤250 (100% MSX1- und 80% EDA-Patienten); TAC >250 (96,9% PAX9- und 90% AXIN2-Patienten). Des Weiteren fand sich ein ungerader TAC-Wert in mindestens einem Quadranten bei 94,3% der EDA-Patienten, aber nur 28,6% der MSX1-Patienten. Ein TAC-Wert von 112 in mindestens in einem Quadranten trat bei 72,7% der PAX9-, jedoch bei keinem der AXIN2 Patienten auf.
Schlussfolgerung
Bisher sind sieben Gene bekannt, die nonsyndromale Oligodontien verursachen können, dies sind in abnehmender Häufigkeit: PAX9, EDA, MSX1, AXIN2, EDARADD, NEMO und KRT17. Auf der Basis des Tooth Agenesis Codes (TAC) war innerhalb des Patientengutes der Metaanalyse ein Zusammenhang zwischen Oligodontie-Phänotyp und Genotyp darstellbar.
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Ruf, S., Klimas, D., Hönemann, M. et al. Genetic background of nonsyndromic oligodontia: a systematic review and meta-analysis. J Orofac Orthop 74, 295–308 (2013). https://doi.org/10.1007/s00056-013-0138-z
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DOI: https://doi.org/10.1007/s00056-013-0138-z