Ectodermal Dysplasia Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
10223 EDA 81479,81479 Order Options and Pricing
EDAR 81479,81479
EDARADD 81479,81479
KRT85 81479,81479
NECTIN1 81479,81479
WNT10A 81479,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
10223Genes x (6)81479 81479(x12) $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 Custom Panel tool.

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

Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing backbone).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing backbone).

Turnaround Time

18 days on average for standard orders or 13 days on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn 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

  • Stela Berisha, PhD, FACMG

Clinical Features and Genetics

Clinical Features

Ectodermal dysplasia (ED) is a clinically and genetically heterogeneous disorder characterized by abnormal development of hair, teeth, nail or sweat glands (Visinoni et al. 2009). ED can be clinically divided into more than 150 subtypes. Hypohidrotic ectodermal dysplasia (HED) is characterized by hypodontia, hypohidrosis and hypotrichosis. The major clinical signs are thin and dry scalp hair, eyelashes and eyebrows, reduced ability to sweat, and congenital missing or abnormal formed teeth. Some patients may have abnormal craniofacial features such as prominent forehead, saddle-back nose, and protruding lips (Visinoni et al. 2009; Wright et al. 2014). HED is currently known to be caused by pathogenic variants in the EDA, EDAR, EDARADD, WNT10A, KRT85 and NECTIN1 genes (Cluzeau et al. 2011; Shimomura et al. 2010; Sözen et al. 2001).

Genetics

Pathogenic variants in EDA cause X-linked HED, while pathogenic variants in EDAR, WNT10A, and EDARADD cause autosomal dominant and recessive forms of ectodermal dysplasia and tooth agenesis. In general, female carriers of EDA pathogenic variants and males and females with autosomal dominant HED have mild clinical features. A variety of pathogenic variants in EDA, EDAR, WNT10A, and EDARADD account for 55-60%, 16%, 15-20% and 1-2% of pathogenic variants identified in HED patients, respectively (Cluzeau et al. 2011). Truncating EDAR pathogenic variants exhibit loss of function, while heterozygous missense pathogenic variants in the functional domain of the EDAR gene may have dominant negative effect (van Der Hout et al. 2008).

The EDA, EDAR, and EDARADD proteins are the key proteins in the EDA-EDAR-EDARADD and the NF-kappa-B pathways, which play a prominent role in the development of ectodermal structures such as hair follicles, sweat glands, and teeth (Cluzeau et al. 2011; Wright et al. 2014). The WNT10A protein is a secreted signaling protein and serves as a ligand for members of the frizzled family of seven transmembrane receptors which are involved in regulation of cell fate and patterning during embryogenesis.

Pathogenic variants in the KRT85 gene cause autosomal recessive ectodermal dysplasia 4, hair/nail type, which is characterized by congenital abnormal development of the hair and nails (Naeem et al. 2006; Shimomura et al. 2010). KRT85 protein coded by KRT85 belongs to the type II keratin gene family, a basic protein which heterodimerizes with type I keratins to form hair and nails. To date, only one small homozygous truncating pathogenic variant (c.1448_1449delCT, p.Pro483Argfs*18) was identified in two affected consanguineous Pakistani families (Shimomura et al. 2010 and Human Gene Mutation Database).

Pathogenic variants in the NECTIN1 gene (also known as PVRL1) cause autosomal recessive cleft lip/palate-ectodermal dysplasia (CLPED1, also known as Zlotogora-Ogur syndrome and Margarita Island ectodermal dysplasia), autosomal recessive Orofacial cleft 7, as well as non-syndromic cleft of the lip/palate. NECTIN1 protein coded by NECTIN1 is a member of the immunoglobin (Ig) superfamily and plays a role in cell–cell adhesion. To date, more than 10 unique pathogenic variants have been reported. They include: missense (7), nonsense (2), small del/dup (3) and splicing (1). No large deletions/duplications have been reported (Sözen et al. 2001; Sözen et al. 2009; Avila et al. 2006, Huma Gene Mutation Database). The 554G>A, p.Trp185* variant is commonly found in non-syndromic sporadic clefting cases in Northern Venezuela, with a carrier frequency of 1 in 26 of the native population in that particular region (Sözen et al. 2001). In addition, heterozygous carriers of the 554G>A, p.Trp185* variant often have a broad and flat upper lip (Avila et al. 2006).

Clinical Sensitivity - Sequencing with CNV PGxome

Mutations in EDA, EDAR, WNT10A and EDARADD together are responsible for ~90% of clinically diagnosed HED patients (Cluzeau et al. 2011). Due to limited publications, clinical sensitivity for the KRT85 and NECTIN1 genes is currently unknown. Analytical sensitivity may be high as the only reported pathogenic variants are detectable by sequencing.

Gross deletions account for ~7% of pathogenic variants found in the EDA gene (Cluzeau et al. 2011; Orstavik et al. 2007; Human Gene Mutation Database). Only one large deletion was reported in each of the EDAR and WNT10A genes (Griggs et al. 2009; Iglesias et al. 2014), and no large deletions or duplications involving KRT85, NECTIN1. and EDARADD have been reported to date (Human Gene Mutation Database).

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 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).

Indications for Test

Candidates for this test are patients with symptoms consistent with HED and tooth agenesis, autosomal recessive form of cleft lip/palate-ectodermal dysplasia (CLPED1, also known as Zlotogora-Ogur syndrome and Margarita Island ectodermal dysplasia), autosomal recessive Orofacial cleft 7, as well as non-syndromic cleft of the lip/palate and the family members of patients who have known EDA, EDAR, WNT10A, EDARADD, KRT85 and NECTIN1 gene mutations.

Genes

Official Gene Symbol OMIM ID
EDA 300451
EDAR 604095
EDARADD 606603
KRT85 602767
NECTIN1 600644
WNT10A 606268
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Name
PGxome®

Citations

  • Avila J.R. et al. 2006. American Journal of Medical Genetics. Part A. 140: 2562-70. PubMed ID: 17089422
  • Cluzeau et al. 2011. PubMed ID: 20979233
  • Griggs B.L. et al. 2009. European Journal of Human Genetics. 17: 30-6. PubMed ID: 18854857
  • Human Gene Mutation Database (Bio-base).
  • Iglesias et al. 2014. PubMed ID: 24901346
  • Naeem M. et al. 2006. Journal of medical genetics. 43: 274-9. PubMed ID: 16525032
  • Shimomura Y. et al. 2010. The Journal of Investigative Dermatology. 130: 892-5 PubMed ID: 19865094
  • Sözen M.A. et al. 2001. Nature Genetics. 29: 141-2. PubMed ID: 11559849
  • Sözen M.A. et al. 2009. Genetic Testing and Molecular Biomarkers. 13: 617-21. PubMed ID: 19715471
  • van der Hout A.H. et al. 2008. European Journal of Human Genetics : Ejhg. 16: 673-9. PubMed ID: 18231121
  • Visinoni A.F. et al. 2009. American Journal of Medical Genetics. Part A. 149A: 1980-2002. PubMed ID: 19681154
  • 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
  • Ørstavik K.H. et al. 2007. American Journal of Medical Genetics. Part A. 143A: 1510-3. PubMed ID: 17568423

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.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

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

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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ORDER OPTIONS

View Ordering Instructions

1) Select Test Method (Backbone)


1) Select Test Type


2) Select Additional Test Options

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

No Additional Test Options are available for this test.

Note: acceptable specimen types are whole blood and DNA from whole blood only.
Total Price: $
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