Branchiootorenal Syndrome via the SIX1 Gene
Summary and Pricing
Test MethodExome Sequencing with CNV Detection
|Test Code||Test Copy Genes||Test CPT Code||Gene CPT Codes Copy CPT Codes||Base Price|
|9165||SIX1||81479||81479,81479||$890||Order Options and Pricing|
|Test Code||Test Copy Genes||Test CPT Code||Gene CPT Codes Copy CPT Code||Base Price|
|9165||SIX1||81479||81479||$890||Order Options and Pricing|
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.
The Sanger Sequencing method for this test is NY State approved.For Sanger Sequencing click here.
For ordering sequencing of targeted known variants, go to our Targeted Variants page.
18 days on average
Clinical Features and Genetics
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 3 (OMIM# 608389) is caused by defects in the SIX1 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.
Branchiootorenal syndrome is an autosomal dominant disorder that can be caused by defects in the EYA1, SIX1 or SIX5 genes (Ruf et al. 2004; Krug et al. 2011). 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).
This test provides full coverage of all coding exons of the SIX1 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 SIX1 variants were found in approximately 4% (10/247) of patients with Branchiootorenal syndrome (Kochhar et al. 2008).
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.
Indications for Test
Candidates for this test are patients with Branchiootorenal syndrome, especially when the EYA1 and SIX5 genes are normal. Testing is also indicated for family members of patients who have known SIX1 mutations.
|Official Gene Symbol||OMIM ID|
- Human Gene Mutation Database (Bio-base).
- Kochhar A, Orten DJ, Sorensen JL, Fischer SM, Cremers CWRJ, Kimberling WJ, Smith RJH. 2008. SIX1 mutation screening in 247 branchio-oto-renal syndrome families: a recurrent missense mutation associated with BOR. Hum. Mutat. 29: 565. PubMed ID: 18330911
- 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
- Ou Z, Martin DM, Bedoyan JK, Cooper ML, Chinault AC, Stankiewicz P, Cheung SW. 2008. Branchiootorenal syndrome and oculoauriculovertebral spectrum features associated with duplication of SIX1, SIX6, and OTX2 resulting from a complex chromosomal rearrangement. Am. J. Med. Genet. A 146A: 2480–2489. PubMed ID: 18666230
- Ruf RG, Xu P-X, Silvius D, Otto EA, Beekmann F, Muerb UT, Kumar S, Neuhaus TJ, Kemper MJ, Raymond RM Jr, Brophy PD, Berkman J, et al. 2004. SIX1 mutations cause branchio-oto-renal syndrome by disruption of EYA1-SIX1-DNA complexes. Proc. Natl. Acad. Sci. U.S.A. 101: 8090-8095. PubMed ID: 15141091
- 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
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.
- 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.