Branchiootorenal Syndrome via the SIX5 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 | |
|---|---|---|---|---|---|
| 8531 | SIX5 | 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
Branchiootorenal syndrome is an autosomal dominant disorder characterized by branchial arch defects (branchial fistulas or cysts), hearing loss (sensorineural, conductive, or mixed hearing loss), and renal anomalies (from mild renal hypoplasia to bilateral renal agenesis) (Smith 2013). Common clinical features include malformations of the outer, middle, and inner ear; preauricular pits and tags, facial asymmetry and palate abnormalities. Some patients develop end-stage renal disease (ESRD) later in life. Branchiootorenal syndrome 2 (OMIM# 610896) is caused by defects of the SIX5 gene. The clinical spectrum of Branchiootorenal syndrome is wide and substantial phenotypic variability can occur even within the same family. Age of onset varies from early childhood to young adulthood.
Genetics
Branchiootorenal syndrome is an autosomal dominant disorder that can be caused by defects of the EYA1, SIX1 or SIX5 genes (Hoskins et al. 2007; Krug et al. 2011). SIX5 has three coding exons that encode a homeodomain-containing transcription factor functioning in the regulation of organogenesis. SIX5 defects represent a minor cause of Branchiootorenal syndrome. To date, only missense pathogenic variants have been found in the SIX5 gene (Human Gene Mutation Database).
Clinical Sensitivity - Sequencing with CNV PGxome
Pathogenic SIX5 variants were found in approximately 5% of patients with Branchiootorenal syndrome (Hoskins et al. 2007) while none were found in another large cohort of 140 patients from 124 families with Branchiootorenal syndrome (Krug et al. 2011).
Thus far, no large deletions or duplications involving the SIX5 gene have been reported (Human Gene Mutation Database).
Testing Strategy
This test provides full coverage of all coding exons of the SIX5 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
Candidates for this test are patients with Branchiootorenal syndrome, especially when the EYA1 and SIX1 genes are normal. Testing is also indicated for family members of patients who have known SIX5 mutations.
Candidates for this test are patients with Branchiootorenal syndrome, especially when the EYA1 and SIX1 genes are normal. Testing is also indicated for family members of patients who have known SIX5 mutations.
Gene
| Official Gene Symbol | OMIM ID |
|---|---|
| SIX5 | 600963 |
| Inheritance | Abbreviation |
|---|---|
| Autosomal Dominant | AD |
| Autosomal Recessive | AR |
| X-Linked | XL |
| Mitochondrial | MT |
Disease
| Name | Inheritance | OMIM ID |
|---|---|---|
| Branchiootorenal Syndrome 2 | 610896 |
Citations
- Hoskins BE, Cramer CH, Silvius D, Zou D, Raymond RM, Orten DJ, Kimberling WJ, Smith RJH, Weil D, Petit C, Otto EA, Xu P-X, et al. 2007. Transcription factor SIX5 is mutated in patients with branchio-oto-renal syndrome. Am. J. Hum. Genet. 80: 800-804. PubMed ID: 17357085
- Human Gene Mutation Database (Bio-base).
- Krug P, Morinière V, Marlin S, Koubi V, Gabriel HD, Colin E, Bonneau D, Salomon R, Antignac C, Heidet L. 2011. Mutation screening of the EYA1, SIX1, and SIX5 genes in a large cohort of patients harboring branchio-oto-renal syndrome calls into question the pathogenic role of SIX5 mutations. Hum. Mutat. 32: 183-190. PubMed ID: 21280147
- Smith RJ. 2013. Branchiootorenal Spectrum Disorders. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong C-T, and Stephens K, editors. GeneReviews™, Seattle (WA): University of Washington, Seattle. PubMed ID: 20301554
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.