Deafness, Autosomal Dominant 10 (DFNA10) via the EYA4 Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
11311 EYA4 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11311EYA481479 81479(x2) $890 Order Options and Pricing

Pricing Comments

Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information. If the Sanger option is selected, CNV detection may be ordered through Test #600.

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).

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

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

  • Ben Dorshorst, PhD

Clinical Features and Genetics

Clinical Features

Autosomal dominant deafness 10 (DFNA10) is a late-onset, progressive nonsyndromic hearing loss disorder that begins in the second to fifth decades, often resulting in severe-to-profound hearing impairment that requires the use of sound amplification. The audioprofile of most nonsyndromic hearing loss cases can be distinct, thus assisting in the development of an evaluation strategy for molecular genetic testing and in generating a prognosis on the rate of hearing loss per year (Hildebrand et al. 2008). Initial stages of DFNA10 generally involve hearing impairment for middle frequency sound, followed by flattening of the audiogram over time that is more pronounced in high-frequency sound (Pfister et al. 2002; Huang et al. 2015). By the sixth decade of life, DFNA10 patients present with severe hearing loss across all frequencies (Tan et al. 2014; Liu et al. 2015). The majority of patients with DFNA10 are equipped with hearing aids by the third or fourth decade. DFNA10 individuals are considered the least responsive to cochlear implants (Hildebrand et al. 2007).

Genetics

DFNA10 is an autosomal dominant hearing disorder that is caused by pathogenic sequence variants in the eyes absent 4 (EYA4) gene, which is located on chromosome 6q23.2 (O'Neill et al. 1996; Borsani et al. 1999). The EYA4 gene consists of 19 coding exons that encode a 639-amino acid transcription factor, which interacts with specific protein families that are involved in early embryonic development, including that of the organ of Corti, tympanic membrane, and the Eustachian tube (Depreaux et al. 2008; Wayne et al. 2001). Disease-causing sequence variants in the EYA4 gene have also been implicated in two other disorders, namely, holoprosencephaly (a birth defect characterized by malformation of the forebrain), and syndromic hearing loss (with dilated cardiomyopathy and mental retardation (Schonberger et al. 2000; Abe et al. 2009). To date, a total of about 20 pathogenic EYA4 sequence variants have been reported, which include 8 missense/nonsense, 2 splicing, 2 small deletions, and 5 small insertions that cause DFNA10, and 1 gross deletion that causes holoprosencephaly, and 2 gross deletions that cause syndromic hearing loss (with dilated cardiomyopathy and mental retardation) (Human Gene Mutation Database).

Clinical Sensitivity - Sequencing with CNV PGxome

The clinical sensitivity of this test has been reported to range from 1% to 12%. For example, three independent research studies conducted in Korea indicated that pathogenic sequence variants in the EYA4 gene accounted for ~1% (1/87) of patients (Kim et al. 2015) and ~12% (1/8) of families (Baek et al. 2012) with autosomal dominant nonsyndromic hearing loss, and in ~3% (1/32, 1/32, and 1/30) families with nonsyndromic hearing loss (Choi et al. 2013; Chang and Choi 2014. Vona et al. 2014).

No large-scale studies have been conducted on gross rearrangements involving the EYA4 gene, thus the clinical sensitivity for these mutations is unclear. One gross deletion (~10.4-Mb in size, which included the promoter and exons 1 and 2 of the EYA4 gene) was detected in a patient with holoprosencephaly (Abe et al. 2009). In another study, one of two families with syndromic sensorineural deafness and dilated cardiomyopathy harbored a 4.8-Mb deletion that overlaps the EYA4 gene (Schonberger et al. 2000).

Testing Strategy

This test provides full coverage of all coding exons of the EYA4 gene 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).

Indications for Test

The ideal EYA4 test candidates are individuals who present with late-onset, progressive, autosomal dominant nonsyndromic hearing loss.

Gene

Official Gene Symbol OMIM ID
EYA4 603550
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Deafness, Autosomal Dominant 10 AD 601316

Citations

  • Abe Y. et al. 2009. Human Mutation. 30: E946-55. PubMed ID: 19606496
  • Baek J.I. et al. 2012. Orphanet Journal of Rare Diseases. 7: 60. PubMed ID: 22938506
  • Borsani G. et al. 1999. Human Molecular Genetics. 8: 11-23. PubMed ID: 9887327
  • Chang M.Y., Choi BY. 2014. Korean Journal of Audiology. 18: 45-9. PubMed ID: 25279224
  • Choi B.Y. et al. 2013. PLoS ONE. 8: e68692. PubMed ID: 23990876
  • Depreux FF. et al. 2008. The Journal of Clinical Investigation. 118: 651-8. PubMed ID: 18219393
  • Hildebrand M.S. et al. 2007. American Journal of Medical Genetics. Part A. 143A: 1599-604. PubMed ID: 17568404
  • Hildebrand M.S. et al. 2008. Genetics in Medicine. 10: 797-804. PubMed ID: 18941426
  • Huang A. et al. 2015. Journal of Translational Medicine. 13: 154. PubMed ID: 25963406
  • Human Gene Mutation Database (Bio-base).
  • Kim Y.R. et al. 2015. Plos One. 10: e0119443. PubMed ID: 25781927
  • Liu F. et al. 2015. Plos One. 10: e0126602. PubMed ID: 25961296
  • O'Neill ME. et al. 1996. Human Molecular Genetics. 5: 853-6. PubMed ID: 8776603
  • Pfister M. et al. 2002. Molecular Medicine (cambridge, Mass.). 8: 607-11. PubMed ID: 12477971
  • Schönberger J. et al. 2000. Circulation. 101: 1812-8. PubMed ID: 10769282
  • Tan M. et al. 2014. International Journal of Molecular Medicine. 34: 1467-72. PubMed ID: 25242383
  • Vona B. et al. 2014. Genetics in Medicine : Official Journal of the American College of Medical Genetics. 16: 945-53. PubMed ID: 24875298
  • Wayne S. et al. 2001. Human Molecular Genetics. 10: 195-200. PubMed ID: 11159937

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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