Branchiootorenal Syndrome via the SIX5 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
8531 SIX5 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8531SIX581479 81479 $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.

A 25% additional charge will be applied to STAT orders. View STAT turnaround times here.

For Reflex to PGxome pricing click here.

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

For Sanger Sequencing click here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

Turnaround Time

18 days on average

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 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).

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.

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

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).

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.

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.

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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