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Cone-Rod Dystrophy (CRD11) via the RAX2 (Qrx) 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
8959 RAX2 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8959RAX281479 81479,81479 $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.

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

Cone-rod dystrophy (CORD/CRD) is a rare hereditary retinal disorder with a worldwide prevalence of ~1 in 40,000. CRD is characterized by dysfunction or degeneration of cone photoreceptors with relative preservation of rod function in the initial stages. The most common symptoms are photophobia and epiphora in bright light, decreased visual acuity, and dyschromatopsia. Fundus changes may vary from mild pigment granularity to a distinct atrophic lesion in the central macula. As the disease progresses, degeneration of rod photoreceptors also occurs and leads to progressive night blindness and peripheral visual field loss (Hamel 2007).

Genetics

Cone-rod dystrophy 11 is an autosomal dominant condition caused by mutations in a novel retinal homeobox 2 gene, RAX2 /QRX (Q50-type) located on chromosome 19p13.3 (Wang 2004). Non syndromic CRD is genetically heterogeneous and exhibits autosomal dominant (ad), autosomal recessive (ar) and, rarely, X-linked (xl) inheritance (Hamel 2007). So far about 25 genes have been implicated in different forms of CRD (RetNet).

Members of the Rx/Rax (retinal homeobox) gene family are shown to be essential for vertebrate eye development. Abnormal expression has been shown to have profound effects on eye development (Pan et al. 2010; Mathers et al. 1997; Bailey et al. 2004). Mouse studies have shown that the embryos carrying dominant null alles of this gene did not form optic cups and therefore did not develop eyes (Mathers et al. 1997). RAX protein is co-expressed along with HES1 (basic helix-loop-helix protein), and NOTCH1 (transmembrane receptor protein) in retinal progenitor cells and promote the formation of Müller glia and bipolar cells (Furukawa et al. 2000). Also, RAX is a transcriptional regulator protein which regulates many photoreceptor-specific genes by binding to their regulatory regions (Kimura et al. 2000). RAX2/QRX protein, which is the closest homologue of RAX (93% identical in the homeodomain) may also play a role in regulation of Rhodopsin and possibly other photoreceptor-specific gene expression. QRX stimulates CRX (cone rod Homeobox) activity and with the help of CRX it also activates NRL (Neural Retina Leucine Zipper), which are also involved with retinal disorders (Wang 2004; Chen et al. 1997). So far, very few pathogenic variations in RAX2 that are associated with autosomal dominant cone-rod dystrophy have been reported (Human Gene Mutation Database).

Clinical Sensitivity - Sequencing with CNV PGxome

A RAX2 mutational screening in a cohort of 322 cone-rod dystrophy (CRD), 107 Leber congenital amaurosis (LCA), 92 age-related macular degeneration (ARMD), 14 autosomal recessive retinitis pigmentosa (ARRP) and 14 autosomal dominant retinitis pigmentosa (ADRP) identified two different heterozygous sequence variations in CRD and AMD patients. These mutations were not found in the pool of 94 control individuals (Wang 2004). Analytical sensitivity is expected to be high because all sequence variations that have been reported are detectable by sequencing.

Testing Strategy

This test provides full coverage of all coding exons of the RAX2 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 cone-rod dystrophy are candidates.

Gene

Official Gene Symbol OMIM ID
RAX2 610362
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Diseases

Name Inheritance OMIM ID
Age-Related Macular Degeneration 6 AD 613757
Cone-Rod Dystrophy 11 AD 610381

Citations

  • Bailey TJ, El-Hodiri H, Zhang L, Shah R, Mathers EH, Jamrich M. 2004. Regulation of vertebrate eye development by Rx genes. The International Journal of Developmental Biology 48: 761–770. PubMed ID: 15558469
  • Chen S, Wang Q-L, Nie Z, Sun H, Lennon G, Copeland NG, Gilbert DJ, Jenkins NA, Zack DJ. 1997. Crx, a novel Otx-like paired-homeodomain protein, binds to and transactivates photoreceptor cell-specific genes. Neuron 19: 1017–1030. PubMed ID: 9390516
  • Furukawa T, Mukherjee S, Bao Z-Z, Morrow EM, Cepko CL. 2000. rax, Hes1, and notch1 Promote the Formation of Müller Glia by Postnatal Retinal Progenitor Cells. Neuron 26: 383–394. PubMed ID: 10839357
  • Hamel CP. 2007. Cone rod dystrophies. Orphanet J Rare Dis 1;2:7. PubMed ID: 17270046
  • Human Gene Mutation Database (Bio-base).
  • Kimura A, Singh D, Wawrousek EF, Kikuchi M, Nakamura M, Shinohara T. 2000. Both PCE-1/RX and OTX/CRX interactions are necessary for photoreceptor-specific gene expression. Journal of Biological Chemistry 275: 1152–1160. PubMed ID: 10625658
  • Mathers PH, Grinberg A, Mahon KA, Jamrich M. 1997. The Rx homeobox gene is essential for vertebrate eye development. Nature 387: 603–607. PubMed ID: 9177348
  • Pan Y, Martinez-De Luna RI, Lou C-H, Nekkalapudi S, Kelly LE, Sater AK, El-Hodiri HM. 2010. Regulation of photoreceptor gene expression by the retinal homeobox (Rx) gene product. Developmental Biology 339: 494–506. PubMed ID: 20060393
  • Wang Q -l. 2004. QRX, a novel homeobox gene, modulates photoreceptor gene expression. Human Molecular Genetics 13: 1025–1040. PubMed ID: 15028672

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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