Branchiootorenal syndrome via the EYA1 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 | |
|---|---|---|---|---|---|
| 11309 | EYA1 | 81406 | 81406,81405 | $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 1 (OMIM# 602588) is caused by defects of the EYA1 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 (Abdelhak et al. 1997; Krug et al. 2011). EYA1 has 16 coding exons that encode a member of the eyes absent (EYA) family of proteins, which may play a role in development of the kidney, branchial arches, eye, and ear. EYA1 defects represent the major cause of Branchiootorenal syndrome, accounting for about 40% of cases. Pathogenic EYA1 variants have been found to include missense and nonsense substitutions, splicing variants, and small indels (Human Gene Mutation Database). Large deletions, duplications and complex rearrangements involving the EYA1 gene have also been commonly reported. These pathogenic variants have been found to cluster within or in the immediate vicinity of the highly conserved 271 amino acid C-terminal region (eyaHR), which is encoded by exons 9 to 16 (Abdelhak et al. 1997).
Clinical Sensitivity - Sequencing with CNV PGxome
Pathogenic EYA1 variants that can be detected via DNA sequencing were found in approximately 30% of patients with Branchiootorenal syndrome (Orten et al. 2008; Krug et al. 2011).
The detection rate of large deletions and duplications involving the EYA1 gene is varied. Multi-exon deletions within EYA1 were found in 15% (3/20) of unrelated patients with Branchiootorenal syndrome (Abdelhak et al. 1997). In another study, 4 out of 5 families were found to have complex rearrangements including large inversion and deletions (Vervoort et al. 2002).
Testing Strategy
This test provides full coverage of all coding exons of the EYA1 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. Testing is also indicated for family members of patients who have known EYA1 mutations.
Candidates for this test are patients with Branchiootorenal syndrome. Testing is also indicated for family members of patients who have known EYA1 mutations.
Gene
| Official Gene Symbol | OMIM ID |
|---|---|
| EYA1 | 601653 |
| Inheritance | Abbreviation |
|---|---|
| Autosomal Dominant | AD |
| Autosomal Recessive | AR |
| X-Linked | XL |
| Mitochondrial | MT |
Disease
| Name | Inheritance | OMIM ID |
|---|---|---|
| Branchiootic syndrome 1 | AD | 602588 |
Citations
- Abdelhak S, Kalatzis V, Heilig R, Compain S, Samson D, Vincent C, Levi-Acobas F, Cruaud C, Merrer M Le, Mathieu M, König R, Vigneron J, et al. 1997. Clustering of mutations responsible for branchio-oto-renal (BOR) syndrome in the eyes absent homologous region (eyaHR) of EYA1. Hum. Mol. Genet. 6: 2247-2255. PubMed ID: 9361030
- Abdelhak S, Kalatzis V, Heilig R, Compain S, Samson D, Vincent C, Weil D, Cruaud C, Sahly I, Leibovici M, Bitner-Glindzicz M, Francis M, et al. 1997. A human homologue of the Drosophila eyes absent gene underlies branchio-oto-renal (BOR) syndrome and identifies a novel gene family. Nat. Genet. 15: 157-164. PMID: PubMed ID: 18330911
- 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
- Orten DJ, Fischer SM, Sorensen JL, Radhakrishna U, Cremers CWRJ, Marres HAM, Camp G Van, Welch KO, Smith RJH, Kimberling WJ. 2008. Branchio-oto-renal syndrome (BOR): novel mutations in the EYA1 gene, and a review of the mutational genetics of BOR. Hum. Mutat. 29: 537-544. PubMed ID: 18220287
- 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
- Vervoort VS, Smith RJH, O’Brien J, Schroer R, Abbott A, Stevenson RE, Schwartz CE. 2002. Genomic rearrangements of EYA1 account for a large fraction of families with BOR syndrome. Eur. J. Hum. Genet. 10: 757-766. PubMed ID: 12404110
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
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2) Select Additional Test Options
No Additional Test Options are available for this test.