Tooth Agenesis Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
3021 AXIN2 81479,81479 Order Options and Pricing
EDA 81479,81479
EDAR 81479,81479
EDARADD 81479,81479
LTBP3 81479,81479
MSX1 81479,81479
PAX9 81479,81479
WNT10A 81479,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
3021Genes x (8)81479 81479 $890 Order Options and Pricing

Pricing Comments

We are happy to accommodate requests for testing single genes in this panel or a subset of these genes. The price will remain the list price. If desired, free reflex testing to remaining genes on panel is available. Alternatively, a single gene or subset of genes can also be ordered via our PGxome Custom Panel tool.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

For Reflex to PGxome pricing click here.

Turnaround Time

18 days on average for standard orders or 14 days on average for STAT orders.

Once a specimen has started the testing process in our lab, the most accurate prediction of TAT will be displayed in the myPrevent portal as an Estimated Report Date (ERD) range. We calculate the ERD for each specimen as testing progresses; therefore the ERD range may differ from our published average TAT. View more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

Tooth agenesis is defined as the congenital absence of one or more teeth excluding third molars with an incidence from 1.6 -6.9% in different populations (Al-Ani et al. 2017). 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 as 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 featured by abnormal development of hair, teeth, nail 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).

Genetics

Pathogenic variants in the EDA gene cause an X-linked form of the ectodermal dysplasia and selective tooth agenesis. Female carriers may have mild ectodermal dysplasia, and approximately 80% of female carriers may have missing teeth (Wright et al. 2014). Ectodysplasin A encoded by the EDA gene plays a key role in the development of ectodermal structures such as hair follicles, sweat glands, and teeth. To date, more than 200 unique pathogenic variants have been reported. They are: missense (51%), truncating (42%), gross deletion (7%), a few small inframe deletions, and only one large insertion (Cluzeau et al. 2011; Human Gene Mutation Database).

Pathogenic variants in the EDAR gene cause autosomal dominant and recessive (also called Rapp-Hodgkin Ectodermal Dysplasia Syndrome) forms of ectodermal dysplasia. The EDAR protein serves as a component in the EDA-EDAR-EDARADD and the NF-kappa-B pathways, which play a key role for the development of ectodermal structures such as hair follicles, sweat glands, and teeth. To date, more than 50 unique pathogenic variants have been reported. They are: missense (53%), truncating (45%), and only one large deletion (Cluzeau et al. 2011; Human Gene Mutation Database).

Pathogenic variants in the EDARADD gene cause autosomal dominant and recessive forms of ectodermal dysplasia and tooth agenesis. The EDARADD protein serves as a component in the EDA-EDAR-EDARADD and the NF-kappa-B pathways, which play a key role in the development of ectodermal structures such as hair follicles, sweat glands, and teeth. To date, about 10 unique pathogenic variants have been reported. They are: 6 missense and 1 small inframe deletion and one small frame-shift duplication (Cluzeau et al. 2011 and Human Gene Mutation Database).

Pathogenic variants in the MSX1 gene cause autosomal dominant ectodermal dysplasia 3, Witkop type and selective tooth agenesis with or without orofacial cleft. To date, more than 50 unique pathogenic variants were reported. They are: missense (64%), truncating (32%), and only one large deletion (Nieminen et al. 2003; Jezewski et al. 2003; Human Gene Mutation Database).

Pathogenic variants in the PAX9 gene cause autosomal dominant selective tooth agenesis type 3. To date, more than 40 unique pathogenic variants have been reported. They are: missense (24), truncating (7) and only a few large deletions/duplications have been reported (Das et al. 2003; Human Gene Mutation Database).

Pathogenic variants in the AXIN2 gene cause autosomal dominant Oligodontia-Colorectal Cancer syndrome (Lammi et al. 2004) and isolated oligodontia (Liu et al. 2000). To date, around 10 unique pathogenic AXIN2 pathogenic variants have been reported. They are: missense (12), truncating (4) (Lammi et al. 2004; Human Gene Mutation Database). No large deletions/duplications have been reported.

Pathogenic variants in the LTBP3 gene cause autosomal recessive Dental Anomalies and Short Stature (Huckert et al. 2015), as well as autosomal recessive Oligodontia (Noor et al. 2009). LTBP3 protein stands for the latent transforming growth factor betas (TGFbs) binding protein 3, an extracellular matrix protein, which modulates the activity of TGFbs. To date, only 10 unique pathogenic LTBP3 pathogenic variants have been reported. They are: missense (1), truncating (9) (Huckert et al. 2015; Human Gene Mutation Database). No large deletions/duplications have been reported.

Pathogenic variants in WNT10A cause at least three types of ectodermal dysplasia: autosomal recessive Odontoonychodermal dysplasia, autosomal recessive Schopf-Schulz-Passarge syndrome, and autosomal dominant Tooth agenesis, selective type 4. The WNT10A protein is a secreted signaling protein and serves as a ligand for members of the frizzled family of seven transmembrane receptors which play key roles in regulation of cell fate and patterning during embryogenesis. To date, more than 60 unique pathogenic variants have been reported. They are: missense (75%), truncating (23%), and one large deletion (Cluzeau et al. 2011; Iglesias et al. 2014; and Human Gene Mutation Database).

Clinical Sensitivity - Sequencing with CNV PGxome

Pathogenic variants in EDA, EDAR, WNT10A and EDARADD together are responsible for ~90% of clinically diagnosed hypohidrotic ectodermal dysplasia patients (Cluzeau et al. 2011). MSX1 pathogenic variants were found in ~2% of patients affected with non-syndromic cleft lip and palate (Jezewski et al. 2003). 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). 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.

Gross deletions account for ~7% of deleterious variants found in EDA and only one large insertion was identified in EDA (Cluzeau et al. 2011; Human Gene Mutation Database). Only a few deletion/duplications were identified in EDAR and WNT10A (Human Gene Mutation Database). Three gross deletions/insertions have been reported in PAX9 that account for ~8% of reported PAX9 pathogenic variants (Human Gene Mutation Database). No large deletion/duplication have been reported in AXIN2 and EDARADD.

Testing Strategy

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.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Indications for Test

Candidates for this test are patients with tooth agenesis.

Genes

Official Gene Symbol OMIM ID
AXIN2 604025
EDA 300451
EDAR 604095
EDARADD 606603
LTBP3 602090
MSX1 142983
PAX9 167416
WNT10A 606268
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Name
PGxome®

Citations

  • Al-Ani A.H. et al. 2017. Biomed Research International. 2017: 9378325. PubMed ID: 28401166
  • Arte S. et al. 2013. Plos One. 8: e73705. PubMed ID: 23991204
  • Cluzeau C. et al. 2011. Human Mutation. 32: 70-2. PubMed ID: 20979233
  • Das P. et al. 2003. American Journal of Medical Genetics Part A. 118A: 35-42. PubMed ID: 12605438
  • Huckert M. et al. 2015. Human Molecular Genetics. 24: 3038-49. PubMed ID: 25669657
  • Human Gene Mutation Database (Bio-base).
  • Iglesias A. et al. 2014. Genetics in Medicine. 16: 922-31. PubMed ID: 24901346
  • Jezewski P.A. et al. 2003. Journal of Medical Genetics. 40: 399-407. PubMed ID: 12807959
  • Lammi L. et al. 2004. American Journal of Human Genetics. 74: 1043-50. PubMed ID: 15042511
  • Liu W. et al. 2000. Nature Genetics. 26: 146-7. PubMed ID: 11017067
  • Nieminen P. et al. 2003. Journal of Dental Research. 82: 1013-7. PubMed ID: 14630905
  • Noor A. et al. 2009. American Journal of Human Genetics. 84: 519-23. PubMed ID: 19344874
  • Tamura M., Nemoto E. 2016. The Japanese Dental Science Review. 52: 75-83. PubMed ID: 28408959
  • Wright J.T. et al. 2014. Hypohidrotic Ectodermal Dysplasia. In: Pagon RA, Adam MP, Ardinger HH, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews(®), Seattle (WA): University of Washington, Seattle. PubMed ID: 20301291

Ordering/Specimens

Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page


Specimen Types

Specimen Requirements and Shipping Details

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ORDER OPTIONS

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2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

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