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, 25 (3), 646-651

Genetic Analysis: Wnt and Other Pathways in Nonsyndromic Tooth Agenesis


Genetic Analysis: Wnt and Other Pathways in Nonsyndromic Tooth Agenesis

Miao Yu et al. Oral Dis.


Tooth agenesis (TA) is one of the most common developmental anomalies that affects the number of teeth. An extensive analysis of publicly accessible databases revealed 15 causative genes responsible for nonsyndromic TA, along with their signaling pathways in Wnt/β-catenin, TGF-β/BMP, and Eda/Edar/NF-κB. However, genotype-phenotype correlation analysis showed that most of the causal genes are also responsible for syndromic TA or other conditions. In a total of 198 different mutations of the 15 genes responsible for nonsyndromic TA, 182 mutations (91.9%) are derived from seven genes (AXIN2, EDA, LRP6, MSX1, PAX9, WNT10A, and WNT10B) compared with the remaining 16 mutations (8.1%) identified in the remaining eight genes (BMP4, DKK1, EDAR, EDARADD, GREM2, KREMEN1, LTBP3, and SMOC2). Furthermore, specificity analysis in terms of the ratio of nonsyndromic TA mutations versus syndromic mutations in each of the aforementioned seven genes showed a 98.2% specificity rate in PAX9, 58.9% in WNT10A, 56.6% in MSX1, 41.2% in WNT10B, 31.4% in LRP6, 23.8% in AXIN2%, and 8.4% in EDA. These findings underscore an important role of the Wnt and Wnt-associated pathways in the genetic etiology of this heterozygous disease and shed new lights on the discovery of novel molecular mechanisms associated with tooth agenesis.

Keywords: Wnt pathway; craniofacial genetics; hypodontia; oligodontia; tooth agenesis.

Conflict of interest statement


The authors declare no competing financial interests.


Figure 1
Figure 1
Three tooth agenesis-associated signaling pathways. Mutated components of these pathways that underlie non-syndromic tooth agenesis in affected human subjects are shown in bolded gene symbols. Genetic interactions between different pathways are briefly discussed in the context. Left panel: the Wnt/β-catenin signaling pathway. Middle panel: the TGF-β/BMP pathway. Right panel: the Eda/Edar/NF-κB pathway. The MSX1 encoded transcriptional repressor is involved in the Wnt ( as well as the BMP4 pathway.
Figure 2
Figure 2
Spectrum of causal mutations in 15 genes responsible for non-syndromic TA. Numbers of mutations in each of the causal genes in affected individuals with non-syndromic TA (in red bar) versus syndromic TA or other conditions (in blue bar) are shown based on the data curated in Human Gene Mutation Database (HGMD), which also are summarized in more details in Supplementary Table 1. More specific genes for non-syndromic TA are clustered, including four Wnt genes (WNT10A, WNT10B, LRP6, and AXIN2) and two genes (MSX1 and PAX9) in the loop of Wnt and BMP4 pathways.

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