Deafness, Autosomal Dominant 4A (DFNA4A) via the MYH14 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
11483 MYH14 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11483MYH1481479 81479 $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.

For Reflex to PGxome pricing click here.

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 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

Deafness, autosomal dominant 4A (DFNA4A) is characterized by progressive, postlingual, sensorineural nonsyndromic hearing loss that begins in the first to third decades of life and eventually results in severe to profound deafness by the fourth decade (Mirgomizadeh et al. 2002; Zong et al. 2012). 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 shows that DFNA4A individuals initially show a downsloping or U-shaped audiogram, indicating more severe hearing loss at high- or mid-frequency sounds, which then later becomes flat by age 40, when the individual progresses to all-frequency hearing loss (Zong et al. 2012; Qing et al. 2014).

Genetics

DFNA4A is an autosomal dominant hearing disorder that is caused by pathogenic sequence variants in the myosin heavy chain 14 (MYH14) gene, which is mainly expressed in the sensory area of the cochlea during embyronic development, as well as in the apical area of intestinal epithelial cells and skeletal muscles (Golomb et al. 2004; Choi et al. 2011). The MYH14 gene is located on chromosome 19q13.33, and consists of 42 coding exons that encode a 2,036-amino acid motor protein (Mirghomizadeh et al. 2002). The MYH14 protein belongs to the myosin II family of ATP-dependent molecular motor proteins that interact with actin microfilaments to regulate cytokinesis, as well as cell motility and polarity (Kim et al. 2005). This 228-kD protein is highly similar to the myosin heavy chain 9 (MYH9), MYH10, and MYH11 proteins based on its highly conserved myosin head domain (Golomb et al. 2004). To date, a total of about 15 pathogenic MYH14 sequence variants have been reported. Most are missense, but chain termination variants have also been reported (Choi et al. 2011; Human Gene Mutation Database).

Clinical Sensitivity - Sequencing with CNV PGxome

The clinical sensitivity of this test has been reported to range from about 2% to 9%. For example, 2.3% (5/216) of Japanese deaf patients tested positive for disease-causing MYH14 sequence variants (Miyagawa et al. 2013). In a German study, 3.3% (1/30) of patients with nonsyndromic hearing loss showed causative MYH14 sequence variants (Vona et al. 2014). In Korea, around 9.1% (1/11) of pediatric patients with sensorineural hearing loss harbored pathogenic sequence variants in the MYH14 gene (Kim et al. 2015).

Testing Strategy

This test provides full coverage of all coding exons of the MYH14 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.

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

The ideal MYH14 test candidates are individuals who present with progressive, postlingual sensorineural nonsyndromic hearing loss that begins in the first to third decades of life and follows an autosomal dominant pattern of inheritance.

Gene

Official Gene Symbol OMIM ID
MYH14 608568
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Deafness, Autosomal Dominant 4 AD 600652

Citations

  • Choi B.O. et al. 2011. Human Mutation. 32: 669-77. PubMed ID: 21480433
  • Golomb E. et al. 2004. The Journal of Biological Chemistry. 279: 2800-8. PubMed ID: 14594953
  • Hildebrand MS. et al. 2008. Genetics in Medicine : Official Journal of the American College of Medical Genetics. 10: 797-804. PubMed ID: 18941426
  • Human Gene Mutation Database (Bio-base).
  • Kim K.Y. et al. 2005. The Journal of Biological Chemistry. 280: 22769-75. PubMed ID: 15845534
  • Kim N.K. et al. 2015. Genetics in Medicine. 213:1-11. PubMed ID: 25719458
  • Mirghomizadeh F. et al. 2002. European Journal of Human Genetics : Ejhg. 10: 95-9. PubMed ID: 11938438
  • Miyagawa M. et al. 2013. PLoS One. 8: e71381. PubMed ID: 23967202
  • Qing J. et al. 2014. Plos One. 9: e109178. PubMed ID: 25289672
  • Vona B. et al. 2014. Genetics in Medicine : Official Journal of the American College of Medical Genetics. 16: 945-53. PubMed ID: 24875298
  • Zong L. et al. 2012. Journal of Genetics and Genomics = Yi Chuan Xue Bao. 39: 653-7. PubMed ID: 23273769

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

loading Loading... ×

ORDER OPTIONS

View Ordering Instructions

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.

Total Price: $
×
Copy Text to Clipboard
×