Branchiootorenal Syndrome Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
10115 EYA1 81406,81405 Order Options and Pricing
SIX1 81479,81479
SIX5 81479,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
10115Genes x (3)81479 81405, 81406, 81479 $890 Order Options and Pricing

Pricing Comments

We are happy to accommodate requests for testing single genes in this panel or a subset of these genes. The price will remain the list price. If desired, free reflex testing to remaining genes on panel is available. Alternatively, a single gene or subset of genes can also be ordered via our PGxome Custom Panel tool.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

For Reflex to PGxome pricing click here.

Turnaround Time

18 days on average for standard orders or 14 days on average for STAT orders.

Once a specimen has started the testing process in our lab, the most accurate prediction of TAT will be displayed in the myPrevent portal as an Estimated Report Date (ERD) range. We calculate the ERD for each specimen as testing progresses; therefore the ERD range may differ from our published average TAT. View 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

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. 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 in 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).

SIX1 has two coding exons that encode a homeobox protein critical to organogenesis. SIX1 defects represent a less frequent cause of Branchiootorenal syndrome. To date, pathogenic SIX1 variants have been found to include missense substitutions, a splicing variant, a small indel and a large deletion (Human Gene Mutation Database).

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 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).

Pathogenic SIX1 variants were found in approximately 4% (10/247) of patients with Branchiootorenal syndrome (Kochhar et al. 2008).

SIX5 pathogenic variants were found in approximately 5% of patients with Branchiootorenal syndrome (Hoskins et al. 2007) while no SIX5 pathogenic variants have been found in another cohort of 140 patients from 124 families with Branchiootorenal syndrome (Krug et al. 2011).

The detection rate of large deletions and duplications involving the EYA1 gene is varied. Multi-exon deletions within EYA1, which can be detected by aCGH, 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 a large inversion and deletions (Vervoort et al. 2002).

A large segmental duplication involving the SIX1 gene was reported in a patient with Branchiootorenal syndrome and oculoauriculovertebral spectrum features (Ou et al. 2008). However, the frequency of exon-level copy number changes has not been reported in a large cohort of patients with Branchiootorenal syndrome.

Thus far, no large deletions or duplications involving the SIX5 gene have been reported (Human Gene Mutation Database).

Testing Strategy

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This panel provides 100% coverage of all coding exons of the genes 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 coverage as ≥20X NGS reads or Sanger sequencing.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Indications for Test

Candidates for this test are patients with Branchiootorenal syndrome.

Genes

Official Gene Symbol OMIM ID
EYA1 601653
SIX1 601205
SIX5 600963
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Name
PGxome®

Citations

  • Abdelhak S. et al. 1997. Human Molecular Genetics. 6: 2247-55. PubMed ID: 9361030
  • Abdelhak S. et al. 1997. Nature Genetics. 15: 157-64. PubMed ID: 9020840
  • Hoskins B.E. et al. 2007. American Journal of Human Genetics. 80: 800-4. PubMed ID: 17357085
  • Human Gene Mutation Database (Bio-base).
  • Kochhar A. et al. 2008. Human Mutation. 29: 565. PubMed ID: 18330911
  • Krug P. et al. 2011. Human Mutation. 32: 183-90. PubMed ID: 21280147
  • Orten D.J. et al. 2008. Human Mutation. 29: 537-44. PubMed ID: 18220287
  • Ou Z. et al. 2008. American Journal of Medical Genetics. Part A. 146A: 2480-9. PubMed ID: 18666230
  • 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 V.S. et al. 2002. European Journal of Human Genetics : Ejhg. 10: 757-66. 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.

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

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ORDER OPTIONS

View Ordering Instructions

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.

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