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Deafness, Autosomal Recessive 35 (DFNB35) via the ESRRB 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
ESRRB 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11303ESRRB81479 81479,81479 $990 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 platform).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing platform).

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

Turnaround Time

3 weeks on average for standard orders or 2 weeks 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.


Genetic Counselors


  • Ben Dorshorst, PhD

Clinical Features and Genetics

Clinical Features

Autosomal recessive deafness 35 (DFNB35) is characterized by prelingual, severe to profound, bilateral nonsyndromic hearing loss affecting all frequencies (Safka Brozkova et al. 2012). 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). DFNB35 individuals also do not elicit acoustic brainstem responses or transient otoacoustic emissions spectra, thereby indicating a disruption of outer hair cell function (Collin et al. 2008). Computerized tomography of the structures of the middle ear of DFNB35 individuals, particularly the temporal bone, is generally normal. Patients diagnosed with DFBN35 usually have no indications of visual problems, kidney failure, or any morphological features that are suggestive of syndromic hearing loss or history of environmental exposure to factors that may cause hearing loss (Lee et al. 2011).


DFNB35 is an autosomal recessive hearing disorder that is caused by pathogenic sequence variants in the estrogen-related receptor beta (ESRRB) gene, which is mainly expressed during inner ear development, as well as in the cochlea postnatally, particularly in the nerve fibers and spiral ganglion cells (Collin et al. 2008). The ESRRB gene is located in chromosome 14q24.3 and consists of 8 coding exons that encode a 508-amino acid protein that is highly similar to the estrogen receptor (Ansar et al. 2003; Misawa and Inoue 2015). The ESRRB protein is also expressed in embryonic stem cells and cancer cells (Ouyang et al. 2009; Amini et al. 2014) and is considered an orphan protein because its ligand is not known (Sanyal et al. 2002). Alternative splicing of the ESRRB gene gives rise to three major isoforms: one short and one long isoform are widely expressed in various human tissues, whereas the longer primate-specific isoform is highly expressed in the testis and cochlea (Zhou et al. 2006; Collin et al. 2008). The two main structures of the ESRRB protein include a ligand-binding domain and a DNA-binding domain (Moras and Gronemeyer 1998).

To date, a total of about 15 pathogenic ESRRB sequence variants have been reported, which include 12 missense/nonsense, 1 small deletion, and 1 small insertion causing hearing loss and 1 splicing variant that has been associated with dental decay (Human Gene Mutation Database; Weber et al. 2014).

Clinical Sensitivity - Sequencing with CNV PGxome

The clinical sensitivity of this test has been reported to range from 1.3% to 1.9%. In a study involving Chinese patients diagnosed with sporadic sensorineural hearing loss, pathogenic sequence variants in the ESRRB gene were detected in 1.3% (1/79) of the patients (Ji et al. 2014). In a multiethnic cohort consisting of families with autosomal recessive nonsyndromic deafness, 1.3% (2/160) of the families were determined to have causative ESRRB sequence variants (Bademci et al. 2015). Approximately 1.9% (3/216) of Japanese patients diagnosed with hearing impairment showed disease-causing sequence variants in the ESRRB gene (Miyagawa et al. 2013).

Testing Strategy

This test provides full coverage of all coding exons of the ESRRB 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 ESRRB test candidates are individuals who present with prelingual, 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 ESRRB.


Official Gene Symbol OMIM ID
ESRRB 602167
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Deafness, Autosomal Recessive 35 AR 608565


  • Amini S. et al. 2014. Anatomy & Cell Biology. 47: 1-11. PubMed ID: 24693477
  • Ansar M. et al. 2003. European Journal of Human Genetics. 11: 77-80. PubMed ID: 12529709
  • Bademci G. et al. 2015. Genetics in Medicine : Official Journal of the American College of Medical Genetics. 0: N/A. PubMed ID: 26226137
  • Collin R.W. et al. 2008. American Journal of Human Genetics. 82: 125-138. PubMed ID: 18179891
  • Hildebrand M.S. et al. 2008. Genetics in Medicine. 10: 797-804. PubMed ID: 18941426
  • Human Gene Mutation Database (Bio-base).
  • Ji H. et al. 2014. Bmc Ear, Nose, and Throat Disorders. 14: 9. PubMed ID: 25342930
  • Lee K. et al. 2011. Genetics Research International. 2011: 368915. PubMed ID: 22567352
  • Misawa A., Inoue S. 2015. Frontiers in Endocrinology. 6: 83. PubMed ID: 26074877
  • Miyagawa M. et al. 2013. PLoS One. 8: e71381. PubMed ID: 23967202
  • Moras D., Gronemeyer H. 1998. Current Opinion in Cell Biology. 10: 384-91. PubMed ID: 9640540
  • Ouyang Z. et al. 2009. Proceedings of the National Academy of Sciences of the United States of America. 106: 21521-6. PubMed ID: 19995984
  • Šafka Brozková D. et al. 2012. International Journal of Pediatric Otorhinolaryngology. 76: 1681-4. PubMed ID: 22951369
  • Sanyal S. et al. 2002. The Journal of Biological Chemistry. 277: 1739-48. PubMed ID: 11705994
  • Weber M.L. et al. 2014. Bmc Medical Genetics. 15: 81. PubMed ID: 25023176
  • Zhou W. et al. 2006. The Journal of Clinical Endocrinology and Metabolism. 91: 569-79. PubMed ID: 16332939


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

If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.

Specimen Types

Specimen Requirements and Shipping Details

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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Note: acceptable specimen types are whole blood and DNA from whole blood only.
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