Usher Syndrome Type 2 and Deafness, Autosomal Recessive 31 (DFNB31) via the WHRN Gene
Summary and Pricing 
Test Method
Exome Sequencing with CNV Detection
| Test Code | Test Copy Genes | Test CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
|---|---|---|---|---|---|
| 11807 | WHRN | 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
Usher syndrome is a clinically heterogeneous disorder characterized by progressive retinitis pigmentosa (RP) and sensorineural hearing impairment, with or without vestibular abnormalities. Three types are recognized based on the age of onset, severity of symptoms, and the vestibular involvement (Smith et al. Am J Med Genet 50:32-38, 1994). Usher syndrome type 2 (USH2) is characterized by mild to severe congenital hearing loss, RP with onset in the teens, and normal vestibular function. Features of RP include night blindness progressing to constriction of the peripheral visual field with eventually loss of central vision, abnormal fundus with bone spicule deposits/attenuated retinal vessels, and abnormal electroretinographic (ERG) findings (Daiger et al. Arch Ophthalmol 125:151-158, 2007).
Genetics
Usher syndrome type 2 (USH2) is a genetically heterogeneous autosomal recessive disease. Variants in three genes (USH2A, GPR98, and WHRN) account for nearly all cases with detectable variants (Eudy et al. Science 280:1753-1757, 1998; Weston et al. Am J Hum Genet 74:357-366, 2004; Mburu et al. Nat Genet 34:421-428, 2003; Keats and Lentz, GeneReviews, 2011). Several WHRN causative variants have been reported and include missense, nonsense, splicing, and small deletions or insertions. The WHRN gene encodes whirlin, which is expressed in the inner ear, retina, and developing brain. Whirlin interacts with several proteins from the Usher protein network, including usherin and GPR98 (Maerker et al. Hum Mol Genet 17: 71-86, 2008).
Clinical Sensitivity - Sequencing with CNV PGxome
This test allows the detection of variants in ~ 5% of patients with USH2 (Keats and Lentz, GeneReviews, 2011).
Testing Strategy
This test provides full coverage of all coding exons of the WHRN 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
Patients with combined congenital sensorineural hearing loss, RP, and normal vestibular function, who do not have USH2A or GPR98 variants and patients with nonsyndromic hearing loss (NSHL). This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in WHRN.
Patients with combined congenital sensorineural hearing loss, RP, and normal vestibular function, who do not have USH2A or GPR98 variants and patients with nonsyndromic hearing loss (NSHL). This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in WHRN.
Gene
| Official Gene Symbol | OMIM ID |
|---|---|
| WHRN | 607928 |
| Inheritance | Abbreviation |
|---|---|
| Autosomal Dominant | AD |
| Autosomal Recessive | AR |
| X-Linked | XL |
| Mitochondrial | MT |
Diseases
| Name | Inheritance | OMIM ID |
|---|---|---|
| Deafness, Autosomal Recessive 31 | AR | 607084 |
| Usher Syndrome, Type 2D | AR | 611383 |
Citations
- Daiger et al. 2007. PubMed ID: 17296890
- Eudy J.D. et al. 1998. Science (new York, N.y.). 280: 1753-7. PubMed ID: 9624053
- Keats BJ, Lentz J. 2011. Usher Syndrome Type II. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJ, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews(®), Seattle (WA): University of Washington, Seattle. PubMed ID: 20301515
- Maerker, T., et.al. (2008). "A novel Usher protein network at the periciliary reloading point between molecular transport machineries in vertebrate photoreceptor cells." Hum Mol Genet 17(1): 71-86. PubMed ID: 17906286
- Mburu P. et al. 2003. Nature Genetics. 34: 421-8. PubMed ID: 12833159
- Smith R.J.H. et al. 1994. American Journal of Medical Genetics. 50: 32-8. PubMed ID: 8160750
- Weston M.D. et al. 2004. American Journal of Human Genetics. 74: 357-66. PubMed ID: 14740321
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
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ORDER OPTIONS
View Ordering Instructions1) Select Test Type
2) Select Additional Test Options
No Additional Test Options are available for this test.