Deafness, Autosomal Recessive 91 (DFNB91) via the SERPINB6 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
4021 SERPINB6 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
4021SERPINB681479 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

Nonsyndromic hearing loss is characterized by difficulty or inability to hear that is not associated with any visible defects involving the external ear, other organs, or any other medical condition. Nonsyndromic hearing loss may be associated with abnormalities involving the middle ear and/or the inner ear (Ciuman 2013; Dodson et al. 2011; Hilgert et al. 2009). At least 70% of cases involving hearing loss are nonsyndromic (Van Camp et al. 1997).

Nonsyndromic hearing loss and deafness due to pathogenic variants in the SERPINB6 gene is associated with postlingual, bilateral, moderate to severe, progressive sensorineural hearing impairment. Onset is in the first or second decade and is characterized by downsloping audiograms. No vestibular abnormalities are present (Sirmaci et al. 2010; Kim et al. 2015).

Genetics

DFNB91 is an autosomal recessive hearing disorder that is caused by pathogenic sequence variants in the serpin family B member 6 (SERPINB6) gene, which is located on chromosome 6p25.2. The SERPINB6 gene spans 28 kb and consists of 6 coding exons that produce a 376 amino acid protein. The SERPINB6 protein is expressed in mice in the crista ampullaris hair cells of the inner ear as well as inner and outer hair cells in the cochlea during embryonic development and postnatally (Sirmaci et al. 2010). SERPINB6 is thought to counteract cytotoxic components of leaking lysosomal proteases caused by normal physiological hearing processes and stress inducing external stimuli to the hair cells of the inner ear (Sirmaci et al. 2010).

Only one nonsense, one splicing and one small deletion variant in the SERPINB6 gene have been reported as pathogenic for hearing loss, all predicted to result in premature protein termination and found in the homozygous or compound heterozygous state in affected individuals (Sirmaci et al. 2010; Kim et al. 2015).

Clinical Sensitivity - Sequencing with CNV PGxome

The clinical sensitivity of this sequencing test is not precisely known. Only one nonsense, one splicing and one small deletion variant in the SERPINB6 gene have been reported as pathogenic for hearing loss, all predicted to result in premature protein termination and found in the homozygous or compound heterozygous state in affected individuals (Sirmaci et al. 2010; Kim et al. 2015). Analytical sensitivity should be high because all reported variants are detectable by sequencing.

No large deletion or duplication variants associated with SERPINB6 have been reported.

Testing Strategy

This test provides full coverage of all coding exons of the SERPINB6 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

Nonsyndromic hearing loss and deafness due to variants in the SERPINB6 gene is suspected in individuals with the following: postlingual, bilateral, moderate to severe, progressive sensorineural hearing impairment beginning in the high frequencies; no related systemic findings identified by medical history and physical examination; and/or a family history of nonsyndromic hearing loss consistent with autosomal recessive inheritance. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in SERPINB6.

Gene

Official Gene Symbol OMIM ID
SERPINB6 173321
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Deafness, Autosomal Recessive 91 AR 613453

Citations

  • Ciuman R.R. 2013. Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. 19: 1195-210. PubMed ID: 24362017
  • Dodson K.M. et al. 2011. American Journal of Medical Genetics. Part A. 155A: 993-1000. PubMed ID: 21465647
  • Hilgert N, Smith RJ, Van Camp G. 2009. Forty-six genes causing nonsyndromic hearing impairment: which ones should be analyzed in DNA diagnostics? Mutat Res 681:189–196. PubMed ID: 18804553
  • Kim N.K. et al. 2015. Genetics in Medicine. 213:1-11. PubMed ID: 25719458
  • Sirmaci A. et al. 2010. American Journal of Human Genetics. 86: 797-804. PubMed ID: 20451170
  • Van Camp G. et al. 1997. American Journal of Human Genetics. 60: 758-64. PubMed ID: 9106521

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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