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Keratoconus and Posterior Polymorphous Corneal Dystrophy via the VSX1 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
VSX1 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8663VSX181479 81479,81479 $990 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 platform).

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

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

For Sanger Sequencing click here.

Turnaround Time

3 weeks on average for standard orders or 2 weeks 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.


Genetic Counselors


  • Dana Talsness, PhD

Clinical Features and Genetics

Clinical Features

Keratoconus (KC; kerato meaning cornea and conus meaning cone) is a common form of corneal dystrophy. Clinically it is characterized by noninflammatory bilateral progressive protrusion of the cornea and central stroma thinning. These often result in high myopia, irregular astigmatism and impairment of visual acuity. Usually it is evident in the second decade of life and eventually stabilizes in the third and fourth decades. Estimated prevalence of KC in the general population is approximately 1: 2,000. KC is most commonly an isolated disorder, though several reports describe it as syndromic and seen in Ehlers-Danlos, Marfan, Apert, Noonan, and Down syndromes (Rabinowitz 1998; Bisceglia 2005; Espandar and Meyer 2010). KC treatment ranges from simple spectacle correction to corneal transplantation (Krachmer et al. 1984).

Posterior polymorphous corneal dystrophy (PPCD) is rare autosomal dominant disorder of the cornea, which is clinically characterized as a nonprogressive disorder affecting both the corneal endothelium (CE) and Descemet’s membrane. IN PPCD, affected patient's CE is often multi-layered due to the presence of desmosomes, tonofilaments, and microvilli. These abnormal cells retain their ability to divide and spread to the trabecular meshwork. 40% of affected patients develop glaucoma necessitating keratoplasty (Cibis et al. 1977; Gwilliam 2005).


KC is clinically and genetically heterogeneous. Both autosomal recessive and dominant (AR and AD) inheritance patterns have been described. AD inheritance is frequently reported in families, showing incomplete penetrance and variable expressivity. Mutations in the VSX1 (visual system homeobox 1, also known as RINX) gene have been associated with two distinct autosomal dominantly inherited corneal dystrophies; KC and PPCD (described in the clinical features). The VSX1 gene, which is located on chromosome 20p11.2 (Gwilliam 2005), is a member of the “paired-like” homeodomain transcription factors. Members of this family are shown to be essential for craniofacial and eye development (Vincent et al. 2013). VSX1, encodes a pair-like homeodomian protein, expressed in the inner nuclear layer of the adult retina (Hayashi et al. 2000). VSX1 protein has been reported to regulate cone bipolar cell differentiation during embryonic development. VSX1 mutations may cause impaired photopic vision (Ohtoshi et al. 2004; Wheeler et al. 2012). So far, about 15 mutations (Missense/nonsense, splicing and small indels) have been reported in VSX1 that are involved in KC and PPCD (Human Gene Mutation Database).

Clinical Sensitivity - Sequencing with CNV PGxome

A VSX1 screening detected causative mutations in 3.1% of KC patients (42/1350) (De Bonis et al. 2011). Another VSX1 mutational analysis detected mutations in 8.7% of Italian KC patients (Bisceglia 2005). Clinical sensitivity cannot be precisely estimated in PPCD patients as it is a rare form of corneal dystrophy. Analytical sensitivity should be high because all mutations reported are detectable by this method. No gross deletions or duplications have been reported so far (Human Gene Mutation Database).

Testing Strategy

This test provides full coverage of all coding exons of the VSX1 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 Keratoconus or Posterior polymorphous corneal dystrophy are candidates.


Official Gene Symbol OMIM ID
VSX1 605020
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Keratoconus 1 AD 148300
Polymorphous Corneal Dystrophy AD 122000


  • Bisceglia L. 2005. VSX1 Mutational Analysis in a Series of Italian Patients Affected by Keratoconus: Detection of a Novel Mutation. Investigative Ophthalmology & Visual Science 46: 3945. PubMed ID: 15623752
  • Cibis GW, Krachmer JA, Phelps CD, Weingeist TA. 1977. The clinical spectrum of posterior polymorphous dystrophy. Arch. Ophthalmol. 95: 15291537. PubMed ID: 302697
  • De Bonis P, Laborante A, Pizzicoli C, Stallone R, Barbano R, Longo C, Mazzilli E, Zelante L, Bisceglia L. 2011. Mutational screening of VSX1, SPARC, SOD1, LOX, and TIMP3 in keratoconus. Molecular vision 17: 2482. PubMed ID: 21976959
  • Espandar L, Meyer J. 2010. Keratoconus: Overview and Update on Treatment. Middle East Afr J Ophthalmol 17: 1520. PubMed ID: 20543932
  • Gwilliam R. 2005. Posterior Polymorphous Corneal Dystrophy in Czech Families Maps to Chromosome 20 and Excludes the VSX1 Gene. Investigative Ophthalmology & Visual Science 46: 44804484. PubMed ID: 16303937
  • Hayashi T, Huang J, Deeb SS. 2000. RINX(VSX1), a novel homeobox gene expressed in the inner nuclear layer of the adult retina. Genomics 67: 128139. PubMed ID: 10903837
  • Human Gene Mutation Database (Bio-base).
  • Krachmer JH, Feder RS, Belin MW. 1984. Keratoconus and related noninflammatory corneal thinning disorders. Surv Ophthalmol 28: 293322. PubMed ID: 6230745
  • Ohtoshi A, Wang SW, Maeda H, Saszik SM, Frishman LJ, Klein WH, Behringer RR. 2004. Regulation of Retinal Cone Bipolar Cell Differentiation and Photopic Vision by the CVC Homeobox Gene< i> Vsx1. Current biology 14: 530536. PubMed ID: 15043821
  • Rabinowitz YS. 1998. Keratoconus. Surv Ophthalmol 42: 297319. PubMed ID: 9493273
  • Vincent AL, Jordan C, Sheck L, Niederer R, Patel DV, McGhee CNJ. 2013. Screening the visual system homeobox 1 gene in keratoconus and posterior polymorphous dystrophy cohorts identifies a novel variant. Mol. Vis. 19: 852860. PubMed ID: 23592923
  • Wheeler J, Hauser MA, Afshari NA, Allingham RR, Liu Y. 2012. The genetics of keratoconus: a review. Microscopy (Oxford, England). PubMed ID: 23795306


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

If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.

Specimen Types

Specimen Requirements and Shipping Details

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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