Tooth Agenesis Panel

Tooth agenesis is defined as the congenital absence of one or more teeth excluding the third molars. It has an incidence from 1.6 -6.9% in different populations (Al-Ani et al. 2017. PubMed ID: 28401166). Tooth agenesis occurs more in permanent teeth than in deciduous teeth, with most patients missing one or two permanent second premolars and upper later incisors. Tooth agenesis can occur in isolated cases, or as a primary feature related to different syndromes. For example, missing teeth is a primary feature of ectodermal dysplasia, which is a clinically and genetically heterogeneous disorder characterized by abnormal development of hair, teeth, nails or sweat glands. The majority of genes related to tooth agenesis are involved in the Wnt signaling pathway that regulates tooth formation and tooth homeostasis (Tamura and Nemoto. 2016. PubMed ID: 28408959).

This panel includes genes associated with a variety of genetic conditions that lead to tooth agenesis or impact tooth health or function and includes ectodermal dysplasia, tooth agenesis with or without orofacial cleft, oligodontia-colorectal cancer syndrome, oligodontia, deafness with dentinogenesis, dentin dysplasia type II, and Shields type II and III dentinogenesis imperfecta. Tooth agenesis disorders are genetically heterogenous and can be inherited in an autosomal dominant, autosomal recessive, and X-linked manner. All types of variants have been reported in the genes within this panel, including missense; nonsense; small deletions, duplications, insertions, and indels; splicing; and regulatory variants. Copy number variants have also been reported in several of these genes (Das et al. 2003. PubMed ID: 12605438; Jezewski et al. 2003. PubMed ID: 12807959; Nieminen et al. 2003. PubMed ID: 14630905; Lammi et al. 2004. PubMed ID: 15042511; Cluzeau et al. 2011. PubMed ID: 20979233; Iglesias et al. 2014. PubMed ID: 24901346; Huckert et al. 2015. PubMed ID: 25669657; Human Gene Mutation Database). 

See individual gene summaries for information about molecular biology of gene products and spectra of pathogenic variants.

Pathogenic variants in EDA, EDAR, WNT10A, and EDARADD are responsible for ~90% of clinically diagnosed hypohidrotic ectodermal dysplasia patients (Cluzeau et al. 2011. PubMed ID: 20979233). MSX1 pathogenic variants were found in ~2% of patients affected with non-syndromic cleft lip and palate (Jezewski et al. 2003. PubMed ID: 12807959). In another study including 7 genes in Wnt signaling pathways (MSX1, AXIN2, PAX9, EDA, EDAR, EDARADD, and WNT10A), 44% of studied probands were found to have a pathogenic variant in one of these genes (Arte et al. 2013. PubMed ID: 23991204). Clinical sensitivity for LTBP3 is currently unknown due to limitations in the medical literature. Analytical sensitivity for LTBP3 may be high because all reported pathogenic variants are detectable by sequencing.

Large deletions account for ~10% of deleterious variants found in EDA and ~1% of deleterious copy number variants are large insertions, duplications, or indels (Human Gene Mutation Database). Only a few large copy number variants have been identified in EDAR and WNT10A (Human Gene Mutation Database). Large copy number variants in PAX9 account for ~8% of reported pathogenic variants (Human Gene Mutation Database). Limited large copy number variants have been reported in the DSPP, EDARADD, LTBP3, and MSX1 genes (Human Gene Mutation Database). To our knowledge, no large copy number variants have been reported in the AXIN2 gene (Human Gene Mutation Database).

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This panel provides 100% coverage of all coding exons of the genes plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).