Deafness, Autosomal Recessive 6 (DFNB6) via the TMIE 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
4031 TMIE 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
4031TMIE81479 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 6 (DFNB6) is a prelingual, severe to profound, stable nonsyndromic hearing loss disorder (Santos et al. 2006). 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). Pure-tone audiometry of DFNB6 individuals generally shows downsloping to flat audiograms, indicating all-frequency hearing loss, with more severe impairment at high frequencies (Chaïb et al. 1996). Affected individuals also do not generate an auditory brainstem response up to 100 decibels. DFNB6 individuals do not have balance problems, nor severe motor dysfunction. Parents of DFNB6 patients are obligate carriers, often showing normal audiometric tests (Chaïb et al. 1996).

Genetics

DFNB6 is an autosomal recessive hearing disorder that is caused by pathogenic sequence variants in the transmembrane inner ear-expressed gene (TMIE) gene, which is located on chromosome 3p21.31 (Fukushima et al. 1995). The TMIE gene consists of four coding exons that encode a 154-amino acid peptide that consists of at least one transmembrane domain (Mitchem et al. 2002). The mature TMIE protein has been localized to the plasma membrane of cochlear cells and serves as a site of interaction for other molecules via its highly charged C-terminal domain (Shin et al. 2010). Previous investigations have also suggested that the TMIE protein plays an important role in signal trafficking between cells, as well as in signal tranduction in the auditory system (Karuppasamy et al. 2011). Functional studies using animal models have shown that pathogenic changes in the TMIE protein result in alterations in sensory hair cells in the cochlea, including defects in stereocilia, which are the apical projections that are involved in mechanoelectrical transduction of sound, thereby resulting in hearing loss (Mitchem et al., 2002; Shen et al. 2008; Gleason et al. 2009; Zhao et al. 2014). To date, a total of about 10 pathogenic TMIE variants have been reported. These variants include both missense and chain termination (nonsense, frameshift and splicing) (Naz et al. 2002; Human Gene Mutation Database).

Clinical Sensitivity - Sequencing with CNV PGxome

The clinical sensitivity of this test has been reported to range up to 8%. In India, 0.09% (1/1,120) of nonsdynromic hearing loss cases harbored disease-causing variants in the TMIE gene (Nishio and Usami 2015). In another study from India, 0.8% (3/374) of families with autosomal recessive, nonsyndromic hearing loss tested positive for disease-causing TMIE variants (Ganapathy et al. 2014). In Iran, 0.7% (1/144) of families with autosomal recessive nonsyndromic hearing loss presented with pathogenic sequence variants in the TMIE gene (Babanejad et al. 2012). In two independent studies conducted in Turkey, 3.4% (1/29; Atik et al. 2015) of families with autosomal recessive nonsyndromic hearing loss and 8.2% (4/49; Duman et al. 2011) of families with nonsyndromic deafness and consanguineous parents were determined to have causative TMIE sequence variants. Approximately 4.1% (7/172) of Jordanian and Pakistani families with autosomal recessive nonsyndromic hearing loss who tested negative for pathogenic sequence variants in the GJB2 gene harbored disease-causing variants in the TMIE gene (Santos et al. 2006).

Testing Strategy

This test provides full coverage of all coding exons of the TMIE 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 TMIE test candidates are individuals who present prelingual, severe to profound, stable, autosomal recessive nonsyndromic hearing loss that does not involve abnormalities of the external or inner ear. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in TMIE.

Gene

Official Gene Symbol OMIM ID
TMIE 607237
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Deafness, Autosomal Recessive 6 AR 600971

Citations

  • Atik T. et al. 2015. Plos One. 10: e0142154. PubMed ID: 26561413
  • Babanejad M. et al. 2012. American Journal of Medical Genetics. Part A. 158A: 2485-92. PubMed ID: 22903915
  • Chaib H. et al. 1996. Human Molecular Genetics. 5: 155-8. PubMed ID: 8789454
  • Duman D. et al. 2011. Genetic Testing and Molecular Biomarkers. 15: 29-33. PubMed ID: 21117948
  • Fukushima K. et al. 1995. Genome Research. 5: 305-8. PubMed ID: 8593615
  • Ganapathy A. et al. 2014. Plos One. 9: e84773. PubMed ID: 24416283
  • Gleason M.R. et al. 2009. Proceedings of the National Academy of Sciences of the United States of America. 106: 21347-52. PubMed ID: 19934034
  • Hildebrand M.S. et al. 2008. Genetics in Medicine. 10: 797-804. PubMed ID: 18941426
  • Human Gene Mutation Database (Bio-base).
  • Karuppasamy S. et al. 2011. Laboratory Animal Research. 27: 339-42. PubMed ID: 22232643
  • Mitchem K.L. et al. 2002. Human Molecular Genetics. 11: 1887-98. PubMed ID: 12140191
  • Naz S. et al. 2002. American Journal of Human Genetics. 71: 632-6. PubMed ID: 12145746
  • Nishio S.Y., Usami S. 2015. The Annals of Otology, Rhinology, and Laryngology. 124 Suppl 1: 49S-60S. PubMed ID: 25788563
  • Santos R.L. et al. 2006. Journal of Molecular Medicine (berlin, Germany). 84: 226-31. PubMed ID: 16389551
  • Shen Y.C. et al. 2008. Developmental Dynamics : an Official Publication of the American Association of Anatomists. 237: 941-52. PubMed ID: 18330929
  • Shin M.J. et al. 2010. Comparative Medicine. 60: 288-94. PubMed ID: 20819378
  • Zhao B. et al. 2014. Neuron. 84: 954-67. PubMed ID: 25467981

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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