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Deafness, Autosomal Dominant 2A (DFNA2A) via the KCNQ4 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
11423 KCNQ4 81479 81479,81479 $990 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11423KCNQ481479 81479,81479 $990 Order Options and Pricing

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 platform).

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

Turnaround Time

3 weeks on average for standard orders or 2 weeks 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

Deafness, Autosomal dominant 2A (DFNA2A) is characterized by progressive, postlingual, symmetric, sensorineural nonsyndromic hearing loss (Coucke et al. 1999). The audioprofile of most autosomal dominant 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 audiometry indicates that DFNA2A generally develops during adolescence or the early 20s and initially only involves high-frequency hearing impairment, which then later progresses to profound all-frequency hearing loss (Nie 2008).

Genetics

DFNA2A is an autosomal dominant hearing disorder that is caused by pathogenic sequence variants in the KCNQ4 gene. KCNQ4 is mainly expressed in the sensory outer hair cells of the cochlea and neurons of the central auditory pathway, and plays a major role in regulating electrical signaling and ionic composition of biologic fluids (Kharkovets et al. 2000). The KCNQ4 gene is located within chromosomal region 1p34 and consists of 14 exons that encode a 695-amino acid protein comprising six transmembrane domains and a P-loop region that forms a potassium-selective channel pore (Coucke et al. 1994; Kubisch et al. 1999).

To date, a total of about 30 pathogenic KCNQ4 sequence variants have been reported, which include missense/nonsense, splicing, small deletions, and small insertions (Human Gene Mutation Database). Previous studies have shown that patients with missense sequence variants in the KCNQ4 gene have earlier disease onset and more profound hearing loss, thereby reflecting a dominant-negative effect, whereas individuals with chain termination KCNQ4 sequence variants generally present late-onset, milder, and pure high-frequency hearing loss, which is indicative of haploinsufficiency (Kamada et al. 2006).

Clinical Sensitivity - Sequencing with CNV PGxome

The clinical sensitivity of this test has been reported to range from about 1 to 6%. For example, disease-causing KCNQ4 variants were detected in 0.8% (1/12) of Taiwanese patients with nonsyndromic deafness (Wu et al. 2013). In two studies involving Japanese deafness patients, 1% (3/216 and 1/1,120) harbored causative KCNQ4 sequence variants (Miyagawa et al. 2013; Nishio and Usami 2015). Another two investigations conducted in Japan indicated that pathogenic sequence variants in the KCNQ4 gene accounted for 6% (1/16 and 19/287) of Japanese families with autosomal dominant nonsyndromic hearing loss (Akita et al. 2001; Naito et al. 2013).

Testing Strategy

This test provides full coverage of all coding exons of the KCNQ4 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 KCNQ4 test candidates are individuals who present with progressive, postlingual, symmetric, sensorineural autosomal dominant nonsyndromic hearing loss.

Gene

Official Gene Symbol OMIM ID
KCNQ4 603537
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Deafness, Autosomal Dominant 2A AD 600101

Citations

  • Akita J. et al. 2001. Journal of Human Genetics. 46: 355-61. PubMed ID: 11450843
  • Coucke P.J. et al. 1994. The New England Journal of Medicine. 331: 425-31. PubMed ID: 8035838
  • Coucke P.J. et al. 1999. Human Molecular Genetics. 8: 1321-8. PubMed ID: 10369879
  • Hildebrand M.S. et al. 2008. Genetics in Medicine. 10: 797-804. PubMed ID: 18941426
  • Human Gene Mutation Database (Bio-base).
  • Kamada F. et al. 2006. Journal of Human Genetics. 51: 455-60. PubMed ID: 16596322
  • Kharkovets T. et al. 2000. Proceedings of the National Academy of Science of the United States of America. 97: 4333-8. PubMed ID: 10760300
  • Kubisch C. et al. 1999. Cell. 96: 437-46. PubMed ID: 10025409
  • Miyagawa M. et al. 2013. PLoS One. 8: e71381. PubMed ID: 23967202
  • Naito T. et al. 2013. PLoS One. 8: e63231. PubMed ID: 23717403
  • Nie L. 2008. Current Opinion in Otolaryngology and Head and Neck Surgery. 16: 441-4. PubMed ID: 18797286
  • Nishio S.Y., Usami S. 2015. The Annals of Otology, Rhinology, and Laryngology. 124 Suppl 1: 49S-60S. PubMed ID: 25788563
  • Wu C.C. et al. 2013. PLoS One. 8: e57369. PubMed ID: 23451214

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

If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.


Specimen Types

Specimen Requirements and Shipping Details

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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ORDER OPTIONS

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View Ordering Instructions

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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.
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