Deafness, Autosomal Recessive 15 (DFNB15) via the GIPC3 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
3477 GIPC3 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
3477GIPC381479 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 15 (DFNB15) is characterized by prelingual, bilateral, severe to profound, nonprogressive, sensorineural nonsyndromic hearing loss that severely affects the development of speech and communication skills of an individual (Van Camp et al. 1997). Individuals diagnosed with DFNB15 do not show signs of vestibular dysfunction, ocular abnormalities, or other syndromic phenotypes (Charizopopulou et al. 2011). 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 DFNB15 individuals generally show a flat audiogram, indicating all-frequency hearing loss (Keller et al. 2011; Siddiqi et al. 2014). This disorder is also known as DFNB72 or DFNB95.

Genetics

DFNB15 is an autosomal recessive hearing disorder that is caused by pathogenic sequence variants in the GIPC PDZ domain-containing family, member 3 (GIPC3) gene. The GIPC3 gene is located on chromosome 19p13.1 and consists of six coding exons. GIPC3 encodes a 312-amino acid protein with three domains, an N-terminal GIPC homology domain, a central PDZ doamin, and a C-terminal GH2 domain (Rehman et al. 2011; Sirmaci et al. 2012). The GIPC3 protein plays a major role in the postnatal maturation of the hair bundle of the outer and inner hair cells, as well as for the long-term survival of hair cells and spiral ganglion by facilitating cellular trafficking, signaling, and recycling of molecules and proteins across the cell membrane (Katoh 2013). Defects in the GIPC3 protein in mouse models have shown poor mechanotransduction in both the inner and outer hair cells, possibly due to defective activity of potassium channels (Charizopoulou et al. 2011). To date, a total of about 12 pathogenic GIPC3 sequence variants have been reported to cause sensorineural nonsyndromic hearing loss, which include 10 missense/nonsense, 1 splicing, and 1 small insertion (Human Gene Mutation Database).

Clinical Sensitivity - Sequencing with CNV PGxome

The clinical sensitivity of this test has been reported to range from 1% to 5%. For example, pathogenic sequence variants in the GIPC3 gene accounted for ~1.3% (2/160; Bademic et al. 2015) of families from a multiethnic cohort and 1.5% (1/65; Ammar-Khodja et al. 2015) of families affected by autosomal recessive nonsyndromic hearing impairment. In Iran, 5% (1/20) of consanguineous families with autosomal recessive nonsyndromic hearing loss harbored disease-causing GIPC3 variants (Diaz-Horta et al. 2012).

Testing Strategy

This test provides full coverage of all coding exons of the GIPC3 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 GIPC3 test candidates are individuals who present with prelingual, bilateral, severe to profound, nonprogressive, sensorineural autosomal recessive nonsyndromic hearing loss that severely affects the development of speech and communication skills. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in GIPC3.

Gene

Official Gene Symbol OMIM ID
GIPC3 608792
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Deafness, Autosomal Recessive 15 AR 601869

Citations

  • Ammar-Khodja F. et al. 2015. Molecular Genetics & Genomic Medicine. 3: 189-96. PubMed ID: 26029705
  • Bademci G. et al. 2015. Genetics in Medicine : Official Journal of the American College of Medical Genetics. 0: N/A. PubMed ID: 26226137
  • Charizopoulou N. et al. 2011. Nature Communications. 2: 201. PubMed ID: 21326233
  • Diaz-Horta O. et al. 2012. Plos One. 7: e50628. PubMed ID: 23226338
  • Hildebrand M.S. et al. 2008. Genetics in Medicine. 10: 797-804. PubMed ID: 18941426
  • Human Gene Mutation Database (Bio-base).
  • Katoh M. 2013. Experimental & Molecular Medicine. 45: e26. PubMed ID: 23743496
  • Keller J.M. et al. 2011. Journal of the Association For Research in Otolaryngology : Jaro. 12: 617-31. PubMed ID: 21594677
  • Rehman AU. et al. 2011. Human Genetics. 130: 759-65. PubMed ID: 21660509
  • Siddiqi S. et al. 2014. Journal of Human Genetics. 59: 683-6. PubMed ID: 25296581
  • Sirmaci A. et al. 2012. Plos One. 7: e32000. PubMed ID: 22363784
  • 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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