Deafness, Autosomal Dominant 25 (DFNA25) via the SLC17A8 Gene
Summary and Pricing
Test Method
Exome Sequencing with CNV DetectionTest Code | Test Copy Genes | Test CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
---|---|---|---|---|---|
4023 | SLC17A8 | 81479 | 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.
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 SLC17A8 gene involves postlingual, high frequency, slowly progressive, sensorineural hearing impairment. Age of onset is highly variable, from the second to sixth decade with incomplete penetrance (Thirlwall et al. 2003; Ruel et al. 2008).
Genetics
DFNA25 is an autosomal dominant hearing disorder that is caused by pathogenic sequence variants in the solute carrier family 17 member 8 (SLC17A8) gene, which is located on chromosome 12q23.1. The SLC17A8 gene spans 69 kb and consists of 12 coding exons that produce a 589 amino acid protein. Only four missense and one small insertion variant in SLC17A8 have been reported as pathogenic for hearing loss (Ruel et al. 2008; Miyagawa et al. 2013; Gonzalez-Garay et al. 2013; Sloan-Heggen et al. 2016; Ryu N et al. 2016).
The SLC17A8 protein transports the neurotransmitter glutamate into synaptic vesicles before it is released into the synaptic cleft. Glutamate is the major excitatory neurotransmitter at the inner hair cell afferent synapse (Puel 1995). The SLC17A8 protein is strongly expressed in cochlear inner hair cells (Ruel et al. 2008; Seal et al. 2008).
Clinical Sensitivity - Sequencing with CNV PGxome
In a study of 1,119 patients with hearing loss in which 440 patients received a genetic diagnosis, only one pathogenic variant in SLC17A8 was detected (Sloan-Heggen et al. 2016). Only four missense and one small insertion variant in SLC17A8 have been reported as pathogenic for hearing loss (Ruel et al. 2008; Miyagawa et al. 2013; Gonzalez-Garay et al. 2013; Sloan-Heggen et al. 2016; Ryu N et al. 2016). Analytical sensitivity should be high because all reported variants are detectable by sequencing.
No large deletion or duplication variants associated with SLC17A8 have been reported as pathogenic for hearing loss.
Testing Strategy
This test provides full coverage of all coding exons of the SLC17A8 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 SLC17A8 gene is suspected in individuals with the following: postlingual, high frequency, slowly progressive, sensorineural hearing impairment; no related systemic findings identified by medical history and physical examination; and/or a family history of nonsyndromic hearing loss consistent with autosomal dominant inheritance.
Nonsyndromic hearing loss and deafness due to variants in the SLC17A8 gene is suspected in individuals with the following: postlingual, high frequency, slowly progressive, sensorineural hearing impairment; no related systemic findings identified by medical history and physical examination; and/or a family history of nonsyndromic hearing loss consistent with autosomal dominant inheritance.
Gene
Official Gene Symbol | OMIM ID |
---|---|
SLC17A8 | 607557 |
Inheritance | Abbreviation |
---|---|
Autosomal Dominant | AD |
Autosomal Recessive | AR |
X-Linked | XL |
Mitochondrial | MT |
Disease
Name | Inheritance | OMIM ID |
---|---|---|
Deafness, Autosomal Dominant 25 | AD | 605583 |
Citations
- Ciuman R.R. 2013. Medical Science Monitor. 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
- Gonzalez-Garay M.L. et al. 2013. Proceedings of the National Academy of Sciences of the United States of America. 110: 16957-62. PubMed ID: 24082139
- Hilgert N. et al. 2009. Mutation Research. 681: 189-96. PubMed ID: 18804553
- Miyagawa M. et al. 2013. PLoS One. 8: e71381. PubMed ID: 23967202
- Puel J.L. 1995. Progress in Neurobiology. 47: 449-76. PubMed ID: 8787031
- Ruel J. et al. 2008. American Journal of Human Genetics. 83: 278-92. PubMed ID: 18674745
- Ryu N. et al. 2016. Bmc Medical Genetics. 17: 6. PubMed ID: 26797701
- Seal R.P. et al. 2008. Neuron. 57: 263-75. PubMed ID: 18215623
- Sloan-Heggen C.M. et al. 2016. Human Genetics. 135: 441-50. PubMed ID: 26969326
- Thirlwall A.S. et al. 2003. Archives of Otolaryngology--head & Neck Surgery. 129: 830-5. PubMed ID: 12925340
- 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
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
ORDER OPTIONS
View Ordering Instructions1) Select Test Type
2) Select Additional Test Options
No Additional Test Options are available for this test.