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Deafness, Autosomal Dominant 15 (DFNA15) via the POU4F3 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
4019 POU4F3 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
4019POU4F381479 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 15 (DFNA15) is a late-onset (postlingual), bilateral, high-frequency, progressive, nonsyndromic hearing loss disorder that begins in the first to third decades and results in severe to profound hearing impairment by the fifth to sixth decades of life. 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). Pure tone audiograms of DFNA15 individuals generally show gently downward-sloping to flat pure tone audiograms, indicating mid-/high-frequency to all-frequency hearing impairment, with a progression rate of around 0.8 decibels/year across most frequencies (Collin et al. 2008: Frydman et al. 2000; Pauw et al. 2008). DFNA15 patients may show variable rates of progression, age of onset, as well as vestibular defects (Freitas et al. 2014). Other rare symptoms include instability, vertigo, and higher risk for falls.

Genetics

DFNA15 is an autosomal dominant hearing disorder that is caused by pathogenic sequence variants in the POU domain, class 4, transcription factor 3 (POU4F3) gene (also known as the BRN3C gene), which is located on chromosome 5q32 (Vahava et al. 1998). The POU4F3 gene consists of two coding exons that encode a 338-amino acid transcription factor, which plays an essential role in the embryonic development of the cochlea, particularly in the maturation, differentiation, as well as survival of inner ear sensory hair cells (Xiang et al. 1995, 1997, 1998; Hertzano et al. 2004; Yoshimura et al. 2014). Functional studies indicate that the POU4F3 protein regulates gene expression of nuclear receptors, neutrophins, cytoplasmic phosphoproteins, and other transcription factors (Hertzano et al. 2004; Clough et al. 2004; Towers et al. 2010; Tornari et al. 2014). To date, a total of about 10 pathogenic POU4F3 sequence variants have been reported, which include 6 missense and 4 frame shift sequence variants that disrupt the functioning of the POU4F3 protein by eliminating its ability to bind to DNA. One entire gene deletion has also been reported (Weiss et al. 2003; Human Gene Mutation Database).

Clinical Sensitivity - Sequencing with CNV PGxome

The clinical sensitivity of this test has been reported to range from 0.5% to 12%. For example, in two independent studies conducted in Japan, disease-causing POU4F3 sequence variants were detected in 0.5% (1/216) of randomly selected deafness patients (Miyagawa et al. 2013) and 6.7% (1/15) of unrelated hearing loss families (Mutai et al. 2013). In Korea, 12.5% (1/8) of families with autosomal dominant nonsyndromic sensorineural hearing loss harbored pathogenic sequence variants in the POU4F3 gene (Baek et al. 2012). In China, causative POU4F3 sequence variants were identified 0.8% (1/125) of deaf patients who tested negative for pathogenic sequence variants in the deafness genes GJB2, SLC26A4, and MT-RNR1 (Yang et al. 2013) and in 4.3% (1/23) of families with nonsyndromic hearing loss (Wei et al. 2014).

Testing Strategy

This test provides full coverage of all coding exons of the POU4F3 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 POU4F3 test candidates are individuals who present with late-onset, bilateral, high-frequency, progressive, autosomal dominant nonsyndromic hearing loss.

Gene

Official Gene Symbol OMIM ID
POU4F3 602460
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Deafness, Autosomal Dominant 15 AD 602459

Citations

  • Baek J.I. et al. 2012. Orphanet Journal of Rare Diseases. 7: 60. PubMed ID: 22938506
  • Clough R.L. et al. 2004. Biochemical and Biophysical Research Communications. 324: 372-81. PubMed ID: 15465029
  • Collin R.W. et al. 2008. Human Mutation. 29: 545-54. PubMed ID: 18228599
  • Freitas É.L. et al. 2014. European Journal of Medical Genetics. 57: 125-8. PubMed ID: 24556497
  • Frydman M. et al. 2000. Archives of Otolaryngology--head & Neck Surgery. 126: 633-7. PubMed ID: 10807331
  • Hertzano R. et al. 2004. Human Molecular Genetics. 13: 2143-53. PubMed ID: 15254021
  • Hildebrand M.S. et al. 2008. Genetics in Medicine. 10: 797-804. PubMed ID: 18941426
  • Human Gene Mutation Database (Bio-base).
  • Miyagawa M. et al. 2013. PLoS One. 8: e71381. PubMed ID: 23967202
  • Mutai H. et al. 2013. Orphanet Journal of Rare Diseases. 8: 172. PubMed ID: 24164807
  • Pauw R.J. et al. 2008. Archives of Otolaryngology--head & Neck Surgery. 134: 294-300. PubMed ID: 18347256
  • Tornari C. et al. 2014. Plos One. 9: e112247. PubMed ID: 25372459
  • Towers E.R. et al. 2011. Journal of Cell Science. 124: 1145-55. PubMed ID: 21402877
  • Vahava O. et al. 1998. Science (new York, N.y.). 279: 1950-4. PubMed ID: 9506947
  • Wei Q. et al. 2014. Journal of Translational Medicine. 12: 311. PubMed ID: 25388789
  • Weiss S. et al. 2003. Molecular and Cellular Biology. 23: 7957-64. PubMed ID: 14585957
  • Xiang M. et al. 1995. The Journal of Neuroscience : the Official Journal of the Society For Neuroscience. 15: 4762-85. PubMed ID: 7623109
  • Xiang M. et al. 1997. Proceedings of the National Academy of Sciences of the United States of America. 94: 9445-50. PubMed ID: 9256502
  • Xiang M. et al. 1998. Development (cambridge, England). 125: 3935-46. PubMed ID: 9735355
  • Yang T. et al. 2013. Orphanet Journal of Rare Diseases. 8: 85. PubMed ID: 23767834
  • Yoshimura H. et al. 2014. Plos One. 9: e92547. PubMed ID: 24676347

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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