Deafness, Autosomal Dominant 22 (DFNA22) and Deafness, Autosomal Recessive 37 (DFNB37) via the MYO6 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
11499 MYO6 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11499MYO681479 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

Autosomal dominant deafness 22 (DFNA22) is characterized by high-frequency, progressive, postlingual sensorineural nonsyndromic hearing loss. The first audiometric abnormalities are generally observed between 6 to 10 years of age. By age 50, individuals with DFNA22 present profound sensorineural deafness involving all frequencies (Hilgert et al. 2008). Some, but not all, DFNA22 patients show vestibular and/or visual dysfunction (Melchionda et al. 2001). DFNA22 patients may also sometimes present with hypertrophic cardiomyopathy (Mohiddin et al. 2004).

Autosomal recessive deafness 37 (DFNB37) is characterized by all-frequency, stable, profound, prelingual sensorineural nonsyndromic hearing loss. DFNB37 patients generally present with vestibular dysfunction, and sometimes with retinitis pigmentosa, mild facial dysmorphism, and/or late ambulation (Ahmed et al. 2003).

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). A flat pure-tone audiogram generally indicates hearing impairment for all frequencies, whereas a down-sloping audiogram indicates high-frequency hearing loss.

Genetics

DFNA22, an autosomal dominant hearing disorder, and DFNB37, an autosomal recessive hearing disorder, are caused by pathogenic sequence variants in the myosin VI (MYO6) gene, which encodes an unconventional actin-based myosin that plays a major role in intracellular vesicle and organelle transport (Rock et al. 2001). The MYO6 gene is located in chromosome 6p14 and is composed of 34 coding exons, spanning a genomic region of approximately 70 kb (Avraham et al. 1995; Ahituv et al. 2000). The MYO6 protein is the only motor molecule that is capable of moving toward the negative end of actin filaments (Altman et all 2004; Ramamurthy et al. 2012). It also participates in endocytic trafficking of clathrin-coated pits, as well as uncoated endocytic vesicles (Naccache et al. 2006). The MYO6 protein is found in the inner and outer hair cells of the sensory epithelium, mainly at the base of the stereocilia where the negative ends of the actin filaments are located (Avraham et al. 1997; Self et al. 1999). It is also found in the retina; therefore, certain patients with pathogenic sequence variants in the MYO6 gene may present symptoms similar to those of Usher syndrome (Ahituv et al. 2000).

To date, less than 30 pathogenic MYO6 sequence variants have been reported, which include missense/nonsense, splicing, small deletions, and small insertions (Human Gene Mutation Database). Around 74% (20/27) or the reported sequence variants are inherited in an autosomal dominant manner, 22% (6/27) are autosomal recessive, and 4% (1/27) are sporadic/de novo.

Clinical Sensitivity - Sequencing with CNV PGxome

The clinical sensitivity of the MYO6 test ranges from 0.6% to 6.3%. For example, pathogenic MYO6 sequence variants were detected in 0.6% (1/160) of Middle Eastern and South American families with autosomal recessive nonsyndromic hearing loss (Bademci et al. 2015). Disease-causing MYO6 variants were responsible for 0.1% (1/1,120) to 1.9% (4/216) of Japanese patients with nonsyndromic hearing loss (Miyagawa et al. 2013; Nishio and Usami 2015). In China, 0.8% (1/125) of deaf probands were determined to have pathogenic MYO6 variants (Yang et al. 2013). Pathogenic sequence variants in the MYO6 gene accounted for 3.3% (1/30) of German patients with nonsyndromic hearing loss (Vona et al. 2014). In Korea, 6.3% (2/32) of families with sensorineural hearing loss were determined to carry causative MYO6 variants (Chang and Choi 2014).

Testing Strategy

This test provides full coverage of all coding exons of the MYO6 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

Ideal MYO6 test candidates are individuals who present with autosomal dominant or recessive nonsyndromic sensorineural hearing loss. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in MYO6.

Gene

Official Gene Symbol OMIM ID
MYO6 600970
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Citations

  • Ahituv N. et al. 2000. Gene. 261: 269-75. PubMed ID: 11167014
  • Ahmed Z.M. et al. 2003. American Journal of Human Genetics. 72: 1315-22. PubMed ID: 12687499
  • Altman D. et al. 2004. Cell. 116: 737-49. PubMed ID: 15006355
  • Avraham K.B. et al. 1995. Nature Genetics. 11: 369-75. PubMed ID: 7493015
  • Avraham K.B. et al. 1997. Human Molecular Genetics. 6: 1225-31. PubMed ID: 9259267
  • Bademci G. et al. 2015. Genetics in Medicine. doi: 10.1038/gim.2015.89. PubMed ID: 26226137
  • Chang M.Y., Choi BY. 2014. Korean Journal of Audiology. 18: 45-9. PubMed ID: 25279224
  • Hildebrand M.S. et al. 2008. Genetics in Medicine. 10: 797-804. PubMed ID: 18941426
  • Hilgert N. et al. 2008. European Journal of Human Genetics. 16: 593-602. PubMed ID: 18212818
  • Human Gene Mutation Database (Bio-base).
  • Melchionda S. et al. 2001. American Journal of Human Genetics. 69: 635-40. PubMed ID: 11468689
  • Miyagawa M. et al. 2013. PLoS One. 8: e71381. PubMed ID: 23967202
  • Mohiddin S.A. et al. 2004. Journal of Medical Genetics. 41: 309-14. PubMed ID: 15060111
  • Naccache S.N. et al. 2006. Proceedings of the National Academy of Sciences of the United States of America. 103: 12735-40. PubMed ID: 16908842
  • Nishio S.Y., Usami S. 2015. The Annals of Otology, Rhinology, and Laryngology. 124 Suppl 1: 49S-60S. PubMed ID: 25788563
  • Ramamurthy B. et al. 2012. Cytoskeleton. 69: 59-69. PubMed ID: 22213699
  • Rock R.S. et al. 2001. Proceedings of the National Academy of Sciences of the United States of America. 98: 13655-9. PubMed ID: 11707568
  • Self T. et al. 1999. Developmental Biology. 214: 331-41. PubMed ID: 10525338
  • Vona B. et al. 2014. Genetics in Medicine. 16: 945-53. PubMed ID: 24875298
  • Yang T. et al. 2013. Orphanet Journal of Rare Diseases. 8: 85. PubMed ID: 23767834

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

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ORDER OPTIONS

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