Comprehensive Vitreoretinopathy Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
7941 ATOH7 81479,81479 Order Options and Pricing
BEST1 81406,81479
CAPN5 81479,81479
COL11A1 81479,81479
COL18A1 81479,81479
COL2A1 81479,81479
COL9A1 81479,81479
COL9A2 81479,81479
CRPPA 81405,81479
CTC1 81479,81479
CTNNB1 81479,81479
FZD4 81479,81479
KCNJ13 81479,81479
KIF11 81479,81479
LRP5 81406,81479
NDP 81404,81403
RCBTB1 81479,81479
RS1 81479,81479
TSPAN12 81479,81479
VCAN 81479,81479
ZNF408 81479,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
7941Genes x (21)81479 81403, 81404, 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

Vitreoretinopathy or Familial Exudative Vitreoretinopathy (FEVR) is an inherited rare ocular disorder characterized by abnormal vascularisation of the peripheral retina. FEVR penetrance is reported to be high, but shows an extremely variable clinical expression even within a family and is clearly asymmetric. At the milder end of the disease spectrum, individuals are asymptomatic or may have a small area of avascularity in the peripheral retina, whereas at the severe end, individuals are legally blind during the first decade of life (Toomes et al. 2004. PubMed ID: 15024691). The secondary retinal pathologies include retinal folds and detachment in association with retinal traction, subretinal or intraretinal exudation, and fibrovascular proliferation at the junction between vascularised and non-vascularised retina. Rarely, retinoschisis and giant retinal tears have been reported (Toomes et al. 2011. PubMed ID: 20301326).

With the advent of gene therapy and other types of treatments, the identification of causative genes and variants is becoming increasingly important.

Please see the following link for clinical trials and management options.

FEVR Clinical trials

Genetics

FEVR is genetically heterogeneous and exhibits autosomal dominant (AD), autosomal recessive (AR) and X-linked (XL) inheritance with AD being the most common mode. Variants in LRP5 cause AR/AD FEVR (EVR4) and variants in NDP cause XL-FEVR (EVR2). Variants in TSPAN12 and FZD4 cause AD FEVR (EVR1 and EVR5 respectively). Together, these four genes are responsible for about 50% of FEVR cases (Poulter et al. 2010. PubMed ID: 20159112).

KIF11 (Hu et al. 2016. PubMed ID: 26472404), COL2A1 (Richards et al. 2002. PubMed ID: 12205109), ZNF408 (Collin et al. 2013. PubMed ID: 23716654), CAPN5 (Rowell et al. 2012. PubMed ID: 23271883) and VCAN (Mukhopadhyay et al. 2006. PubMed ID: 16877430) have also been reported to be associated with AD Vitreoretinopathy.

LRP5 (low-density lipoprotein 5), FZD4 (frizzled 4), NDP (norrin), and TSPAN12 (tetraspanin-12) encoded proteins act as ligand and receptors in the Wnt signaling pathway, suggesting a critical role for this pathway in eye organogenesis and angiogenesis (Warden et al. 2007. PubMed ID: 18097984; Nikopoulos et al. 2010. PubMed ID: 20340138; Gilmour. 2015. PubMed ID: 25323851). Perturbations in the Wnt signaling pathway due to pathogenic variants in LRP5, FZD4 and NDP have also been linked to several other degenerative diseases. For instance, pathogenic variants in LRP5 cause AR osteoporosis-pseudoglioma syndrome, AD Osteosclerosis type1 and AD bone mineral density variability 1. Pathogenic variants in NDP cause a severe phenotype called Norrie disease and Coats disease. Pathogenic variants in FZD4 cause Retinopathy of prematurity (ROP). It has been shown that pathogenic variants in FZD4, LRP5 and NDP account for a small percentage of (3-12%) of ROP cases (Shastry. 2010. PubMed ID: 20738858; Shastry et al. 1997. PubMed ID: 9152134; Hiraoka et al. 2010. PubMed ID: 21151595), which explains the phenotypic similarities in FEVR and ROP and also suggests that the Wnt pathway is defective in both disorders.

Missense, splicing, small deletions/insertions, and gross deletions have been reported in these genes (listed in the below table) associated with Vitreoretinopathies (Human Gene Mutation Database). Narumi et al. reported gross deletions in LRP5 (Narumi et al. 2010. PubMed ID: 20034086). One gross deletion in TSPAN12 and none in FZD4 have been reported (Human Gene Mutation Database). A complete COL2A1 gene deletion has also been reported (Richards et al. 2010. PubMed ID: 20513134).

The three most frequently reported pathogenic variants are NDP c. 362G >A (p. Arg121Gln), FZD4 c. 313A >G (p.Met105Val), and c.1282_1285delGACA (p. Asp428Serfs*2) (Xiao et al. 2019. PubMed ID: 31827910).

Gene Pattern of Inheritance
FZD4 AD
LRP5 AD and AR
TSPAN12 AD
NDP X-linked
COL2A1 AD
VCAN AD
ZNF408 AD
CAPN5 AD
KIF11 AD
CTNNB1 AD
ATOH7 AR
RCBTB1 AR
CRPPA/ISPD AR
BEST1 AD
COL11A1 AD
COL18A1 AR
COL9A1 AR
COL9A2 AR
CTC1 AR
KCNJ13 AR
RS1 XL

See individual gene summaries for more information about molecular biology of gene products and spectra of pathogenic variants.

Clinical Sensitivity - Sequencing with CNV PGxome

A mutation analysis in 20 affected families identified FZD4 pathogenic variants in 8 families (40%), LRP5 pathogenic variants in 2 families (10%), and NDP pathogenic variants in 2 families (10%) (Boonstra et al. 2009. PubMed ID: 19324841). In another study, Toomes et al. reported that together LRP5 (15%) and FZD4 (20%) account for 35% of FEVR cases (Toomes et al. 2004. PubMed ID: 15024691), whereas Nallathambi et al. reported that pathogenic variants in FZD4 were seen in 5.6% of the clinically diagnosed FEVR Indian patients (Nallathambi et al. 2006. PubMed ID: 17093393). Poulter et al. reported that the TSPAN12 gene alone accounted for 10% of FEVR cases (Poulter et al. 2010. PubMed ID: 20159112). According to Riveiro-Alvarez et al., ~85% of the patients clinically diagnosed with Norrie Disease have pathogenic sequence variants in NDP and the rest of the 15% had intragenic and submicroscopic deletions involving NDP and adjacent regions (Riveiro-Alvarez et al. 2005. PubMed ID: 16163268).

Testing Strategy

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

This panel typically provides 99.9% 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

EVR patients and patients with EVR symptoms with overlapping bone mass disorders are good candidates.

Genes

Official Gene Symbol OMIM ID
ATOH7 609875
BEST1 607854
CAPN5 602537
COL11A1 120280
COL18A1 120328
COL2A1 120140
COL9A1 120210
COL9A2 120260
CRPPA 614631
CTC1 613129
CTNNB1 116806
FZD4 604579
KCNJ13 603208
KIF11 148760
LRP5 603506
NDP 300658
RCBTB1 607867
RS1 300839
TSPAN12 613138
VCAN 118661
ZNF408 616454
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Name
PGxome®

Citations

  • Boonstra et al. 2009. PubMed ID: 19324841
  • Collin et al. 2013. PubMed ID: 23716654
  • Gilmour. 2015. PubMed ID: 25323851
  • Hiraoka et al. 2010. PubMed ID: 21151595
  • Hu et al. 2016. PubMed ID: 26472404
  • Human Gene Mutation Database (Bio-base).
  • Mukhopadhyay et al. 2006. PubMed ID: 16877430
  • Nallathambi et al. 2006. PubMed ID: 17093393
  • Narumi et al. 2010. PubMed ID: 20034086
  • Nikopoulos et al. 2010. PubMed ID: 20340138
  • Poulter et al. 2010. PubMed ID: 20159112
  • Richards et al. 2002. PubMed ID: 12205109
  • Richards et al. 2010. PubMed ID: 20513134
  • Riveiro-Alvarez et al. 2005. PubMed ID: 16163268
  • Rowell et al. 2012. PubMed ID: 23271883
  • Shastry et al. 1997. PubMed ID: 9152134
  • Shastry et al. 2010. PubMed ID: 20738858
  • Toomes et al. 2004. PubMed ID: 15024691
  • Toomes et al. 2011. PubMed ID: 20301326
  • Warden et al. 2007. PubMed ID: 18097984
  • Xiao et al. 2019. PubMed ID: 31827910

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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