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Wagner Syndrome via the VCAN 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
11791 VCAN 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11791VCAN81479 81479(x2) $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.

Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing backbone).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing backbone).

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 13 days 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.

EMAIL CONTACTS

Genetic Counselors

Geneticist

  • Dana Talsness, PhD

Clinical Features and Genetics

Clinical Features

Wagner syndrome (WS) is a rare, dominantly inherited eye disorder. WS is clinically characterized by optically empty vitreous cavity with avascular strands, membranes and/or veils, which are the pathological hallmark features of WS (Graemiger et al. 1995; Kloeckener-Gruissem and Amstutz 2012). Additional and common (≤60% of affected Individuals) symptoms include myopia, pre-senile cataract, progressive night blindness and chorioretinal atrophy. The WS clinical features are usually evident during early adolescence, but can also occur in early childhood (as early as two years). The advance stages of WS symptoms are retinal traction and retinal detachment, which eventually leads to vision loss. Systemic abnormalities are absent in WS, that helps to distinguish WS from Stickler syndrome (STL). The overlapping clinical features in WS and STL are myopia, presenile cataract, vitreous degeneration, radial perivascular retinal degeneration, and tractional retinal detachments (Kloeckener-Gruissem et al. 2013; Meredith et al. 2007; Ronan 2009; Mukhopadhyay et al. 2006; Kloeckener-Gruissem and Amstutz 2012).

Genetics

Wagner syndrome is a dominantly inherited eye disorder caused by mutation in the VCAN gene.VCAN (previously known as CSPG2) encodes a chondroitin sulfate (CS) proteoglycan termed versican, which is an extracellular matrix protein and a major constituent of the human vitreous (Ronan 2009; Brézin et al. 2011; Kloeckener-Gruissem et al. 2013). In the vitreous, versican forms large protein aggregates by binding to hyaluronan and link proteins, which is important for maintaining structural integrity (Miyamoto et al. 2005). VCAN, which is located on 5q14.3, is the only gene associated with WS. So far, about 15 pathogenic variations in VCAN (missense, nonsense, splicing and gross insertions/duplications) have been associated with WS (Human Gene Mutation Database; Shi et al. 2004). VCAN mutational screening in a French (19 affected and 19 unaffected) and a British family (3 affected) detected VCAN pathogenic variants in all affected (19) members of the French family, which was absent in all unaffected (19) members. Similarly, all affected British family members had VCAN mutations (Kloeckener-Gruissem et al. 2013).

Clinical Sensitivity - Sequencing with CNV PGxome

In ten out of twelve families diagnosed with VCAN-related vitreoretinopathy, mutations in the VCAN gene were identified (Kloeckener-Gruissem and Amstutz 2012), which indicates that clinical sensitivity is high. Analytical sensitivity is also expected to be high as the great majority of reported mutations are detectable by direct sequencing of genomic DNA and only one gross deletion in VCAN has been reported so far (Human Gene Mutation Database).

Testing Strategy

This test provides full coverage of all coding exons of the VCAN 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

All patients with symptoms suggestive of Wagner syndrome or erosive vitreoretinopathy are candidates.

Gene

Official Gene Symbol OMIM ID
VCAN 118661
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Wagner Syndrome AD 143200

Citations

  • Brézin AP, Nedelec B, Barjol A, Rothschild P-R, Delpech M, Valleix S. 2011. A new VCAN/versican splice acceptor site mutation in a French Wagner family associated with vascular and inflammatory ocular features. Molecular vision 17: 1669. PubMed ID: 21738396
  • Graemiger RA, Niemeyer G, Schneeberger SA, Messmer EP. 1995. Wagner vitreoretinal degeneration. Follow-up of the original pedigree. Ophthalmology 102: 1830–1839. PubMed ID: 9098284
  • Human Gene Mutation Database (Bio-base).
  • Kloeckener-Gruissem B, Amstutz C. 2016. VCAN-Related Vitreoretinopathy. In: Pagon RA, Adam MP, Ardinger HH, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews(®), Seattle (WA): University of Washington, Seattle. PubMed ID: 20301747
  • Kloeckener-Gruissem B, Neidhardt J, Magyar I, Plauchu H, Zech J-C, Morlé L, Palmer-Smith SM, MacDonald MJ, Nas V, Fry AE. 2013. Novel VCAN mutations and evidence for unbalanced alternative splicing in the pathogenesis of Wagner syndrome. European Journal of Human Genetics 21: 352–356. PubMed ID: 22739342
  • Meredith SP, Richards AJ, Flanagan DW, Scott JD, Poulson AV, Snead MP. 2007. Clinical characterisation and molecular analysis of Wagner syndrome. British Journal of Ophthalmology 91: 655–659. PubMed ID: 17035272
  • Miyamoto T, Inoue H, Sakamoto Y, Kudo E, Naito T, Mikawa T, Mikawa Y, Isashiki Y, Osabe D, Shinohara S, Shiota H, Itakura M. 2005. Identification of a novel splice site mutation of the CSPG2 gene in a Japanese family with Wagner syndrome. Invest. Ophthalmol. Vis. Sci. 46: 2726–2735. PubMed ID: 16043844
  • Mukhopadhyay A. et al. 2006. Investigative Ophthalmology & Visual Science. 47: 3565-72.  PubMed ID: 16877430
  • Ronan SM. 2009. Mutational Hot Spot Potential of a Novel Base Pair Mutation of the CSPG2 Gene in a Family With Wagner Syndrome. Archives of Ophthalmology 127: 1511. PubMed ID: 19901218
  • Shi S, Grothe S, Zhang Y, O’Connor-McCourt MD, Poole AR, Roughley PJ, Mort JS. 2004. Link Protein Has Greater Affinity for Versican than Aggrecan. J. Biol. Chem. 279: 12060–12066. PubMed ID: 14724283

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


Specimen Types

Specimen Requirements and Shipping Details

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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ORDER OPTIONS

View Ordering Instructions

1) Select Test Method (Backbone)


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.

Note: acceptable specimen types are whole blood and DNA from whole blood only.
Total Price: $
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