Branchiootorenal syndrome via the EYA1 Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
11309 EYA1 81406 81406,81405 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11309EYA181406 81405, 81406 $890 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.

For Reflex to PGxome pricing click here.

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing 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. 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.

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. 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.

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

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2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

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