DNA icon

Deafness, Autosomal Recessive 8 (DFNB8) and Deafness, Autosomal Recessive 10 (DFNB10) via the TMPRSS3 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
4271 TMPRSS3 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
4271TMPRSS381479 81479,81479 $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.

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 8 (DFNB8) and autosomal recessive deafness 10 (DFNB10) are characterized by progressive, sensorineural nonsyndromic hearing loss. The onset of DFNB8 is postlingual (age range: 10-12 years), whereas that of DFNB10 is prelingual (Wattenhofer et al. 2002). 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. DFNB8 patients generally show flat audiogram configurations, indicating hearing impairment at all frequencies, whereas DFNB10 patients have down-sloping audiogram configurations, demonstrating high-frequency impairment that later progresses to include low- and mid-frequency hearing loss (Weegerink et al. 2011). Patients diagnosed with DFNB8/10 are generally considered good candidates for electric acoustic stimulation (Miyagawa et al. 2015).

Genetics

DFNB8/10 is an autosomal recessive hearing disorder that is caused by pathogenic sequence variants in the transmembrane protease, serine 3 (TMPRSS3) gene. TMPRSS3 encodes a 478-amino acid protein that is expressed in the hair cells of the cochlea, as well as in the brain, liver, spleen, lungs, and muscles (Guipponi et al. 2002). The TMPRSS3 gene has been localized to chromosome 21q22.3 and consists of 13 exons that span approximately 24 kb (Veske et al. 1993; Scott et al. 2001). The TMPRSS3 protein is structurally characterized by four domains, namely, an N-terminal transmembrane domain, a low-density lipoprotein (LDL) receptor A domain, a scavenger receptor cysteine-rich domain, and a C-terminal serine protease domain (Fasquelle et al. 2011). To date, a total of about 50 pathogenic sequence variants have been reported in the TMPRSS3 gene, which include missense/nonsense, splicing, regulatory, small deletions, small insertions, and complex rearrangements (Human Gene Mutation Database).

Clinical Sensitivity - Sequencing with CNV PGxome

The clinical sensitivity of this test has been reported to range from 0.1% to 5%. For example, pathogenic sequence variants in the TMPRSS3 gene accounted for 0.1%-2.8% of Japanese hearing loss patients (Miyagawa et al. 2013; Miyagawa et al. 2015; Nishio and Usami 2015). About 0.4% (2/448) of Caucasian deaf patients from Spain, Italy, Greece, and Australia who tested negative for GJB2 pathogenic sequence variants harbored causative variants in the TMPRSS3 gene (Wattenhofer et al. 2002). Approximately 0.8% (3/384) of Indian families with nonsyndromic hearing were determined to carry pathogenic TMPRSS3 sequence variants (Ganapathy et al. 2014). In Turkey, 2% (1/49) of deaf children born to consanguineous families and GJB2-, GJB6-, and MTRNR1-negative for pathogenic sequence variants were determined to harbor disease-causing sequence variants in the TMPRSS3 gene (Duman et al. 2011). In Palestine, 5% (1/20) of families with prelingual nonsyndromic hearing loss harbored causative TMPRSS3 sequence variants (Shahin et al. 2010).

Testing Strategy

This test provides full coverage of all coding exons of the TMPRSS3 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 TMPRSS3 test candidates are individuals who present with progressive, nonsyndromic hearing loss. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in TMPRSS3.

Gene

Official Gene Symbol OMIM ID
TMPRSS3 605511
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Deafness, Autosomal Recessive 8/10 AR 601072

Citations

  • Duman D. et al. 2011. Genetic Testing and Molecular Biomarkers. 15(1-2): 29-33. PubMed ID: 21117948
  • Fasquelle L. et al. 2011. Journal of Biological Chemistry. 286: 17383-17397. PubMed ID: 21454591
  • Ganapathy A. et al. 2014. PLoS ONE. 9(1): e84773. PubMed ID: 24416283
  • Guipponi M. et al. 2002. Human Molecular Genetics. 11(23): 2829-836. PubMed ID: 12393794
  • Human Gene Mutation Database (Bio-base).
  • Miyagawa M. et al. 2013. PLoS ONE. 8(8): e71381. PubMed ID: 23967202
  • Miyagawa M. et al. 2015. Annals of Otology, Rhinology, and Laryngology. 124(5S): 193S-204S. PubMed ID: 25770132
  • Nishio S.Y., Usami S. 2015. Annals of Otology, Rhinology, and Laryngology. 124(5S): 49S-60S. PubMed ID: 25788563
  • Scott H. et al. 2001. Nature Genetics. 27: 59-63. PubMed ID: 11137999
  • Shahin H. et al. 2010. European Journal of Human Genetics. 18(4): 407-13. PubMed ID: 19888295
  • Veske A. et al. 1993. Human Molecular Genetics. 5: 165-8. PubMed ID: 8789456
  • Wattenhofer M. et al. 2002. Journal of Molecular Medicine. 80: 124-31. PubMed ID: 11907649
  • Weegerink N.J.D. et al. 2011. JARO. 12: 753-66. PubMed ID: 21786053

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

loading Loading... ×

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: $
×
Copy Text to Clipboard
×