Deafness, Autosomal Recessive 3 (DFNB3) via the MYO15A 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
11493 MYO15A 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11493MYO15A81479 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 recessive deafness 3 (DFNB3) is characterized by severe to profound, stable, prelingual, sensorineural nonsyndromic hearing loss. This disorder was initially reported in 1995 in a population of 2,200 villagers in Bengkala, Bali in Indonesia, in which 45 individuals were deaf (Winata et al. 1995). Due to the high incidence of deafness in this Balinese village for at least seven generations, the first cohort of deaf individuals developed a unique and complex sign language that is known by majority of the Bengkala community. Subsequent studies have identified individuals with DFNB3 hearing loss in various Asian, European, Middle Eastern, and South American countries (Lezirovitz et al. 2008; Duman et al. 2011; Fattahi et al. 2012; Ammar-Khodja et al. 2015).

Genetics

DFNB3 is an autosomal recessive hearing disorder that is caused by pathogenic sequence variants in the MYO15A gene. MYO15A encodes a 3,530-amino protein called myosin-XV that plays a critical role in the formation of stereocilia in the cochlear hair cells (Anderson et al. 2000). This MYO15A protein comprises an N-terminal motor domain, two light-chain binding IQ motifs, and a tail region that consists of a MyTH4 and a line-like domain. The MYO15A protein is also expressed in the brain, ovary, testis, kidney, and pituitary gland. The MYO15A gene is 71 kb in size, located on chromosome 17p11.2, and consists of 66 exons (Liang et al. 1998). Functional studies have shown that the MYO15A protein interacts with the whirlin protein at the tips of stereocilia of the cochlear hair cells, which in turn regulates stereocilia elongation (Belyantseva et al. 2003). To date, about 100 pathogenic MYO15A sequence variants have been reported, which include missense/nonsense, splicing, small deletions, small insertions, small indels, and complex rearrangements (Human Gene Mutation Database).

Clinical Sensitivity - Sequencing with CNV PGxome

The clinical sensitivity of this test ranges from 0.98% to 15%, depending on the ethnicity of the patient. For example, causative sequence variants in the MYO15A gene account for 0.98% (11/1,120) of Japanese patients with hearing loss (Miyagawa et al. 2015). Pathogenic sequence variants in the MYO15A gene are responsible for 1.5% (1/65) of Algerian families affected by autosomal recessive forms of nonsyndromic hearing impairment (Amman-Khodja et al. 2015). In Iran, 5.71% (8/140) families who were GJB2 variant-negative, mostly consanguineous, with at least two affected children, were determined to have pathogenic sequence variants in the MYO15A gene (Fattahi et al. 2012). A study involving Turkish families with at least three affected children born to consanguineous parents showed that 12.2% (6/49) of the families carried causative sequence variants in the MYO15A gene (Duman et al. 2011). In a collaborative research study involving Iranian and Turkish unrelated consanguineous families with autosomal recessive nonsyndromic hearing loss, 15% (3/20) of the families harbored pathogenic sequence variants in the MYO15A gene (Diaz-Horta et al. 2012).

Testing Strategy

This test provides full coverage of all coding exons of the MYO15A 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 MYO15A test candidates are individuals who present with congenital, bilateral, severe to profound, autosomal recessive nonsyndromic hearing loss. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in MYO15A.

Gene

Official Gene Symbol OMIM ID
MYO15A 602666
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Deafness, Autosomal Recessive 3 AR 600316

Citations

  • Ammar-Khodja F. et al. 2015. Molecular Genetics & Genomic Medicine. 3: 189-96. PubMed ID: 26029705
  • Anderson D.W. et al. 2000. Human Molecular Genetics. 9: 1729-38. PubMed ID: 10915760
  • Belyantseva I.A. et al. 2003. Proceedings of the National Academy of Sciences of the United States of America. 100: 13958-63. PubMed ID: 14610277
  • Diaz-Horta O. et al. 2012. Plos One. 7: e50628. PubMed ID: 23226338
  • Duman D. et al. 2011. Genetic Testing and Molecular Biomarkers. 15: 29-33. PubMed ID: 21117948
  • Fattahi Z. et al. 2012. American Journal of Medical Genetics. Part A. 158A: 1857-64. PubMed ID: 22736430
  • Human Gene Mutation Database (Bio-base).
  • Lezirovitz K. et al. 2008. European Journal of Human Genetics. 166: 89-96. PubMed ID: 17851452
  • Liang Y. et al. 1998. American Journal of Human Genetics. 62:904-15. PubMed ID: 9529344
  • Miyagawa M. et al. 2015. The Annals of Otology, Rhinology, and Laryngology. 124 Suppl 1: 1585-685. PubMed ID: 25792667
  • Winata S. et al. 1995. Journal of Medical Genetics. 32: 336-343. PubMed ID: 7616538

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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