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Retinitis Pigmentosa via the RP1 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
11623 RP1 81404 81404,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11623RP181404 81404,81479 $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

Retinitis pigmentosa (RP) or rod cone dystrophies (RCDs) represent a group of hereditary retinal dystrophies with a worldwide prevalence of ~1 in 4000 (Booij et al. 2005). RP is clinically characterized by retinal pigment deposits visible on fundus examination, nyctalopia, followed by progressive degeneration of the photoreceptors, which eventually leads to blindness (van Soest et al. 1999).

Genetics

Nonsyndromic and syndromic RP is remarkably heterogeneous both clinically and genetically. RP exhibits autosomal dominant (ad, 15%-25% of the cases), autosomal recessive (ar, 5%-20% of the cases) or X-linked (XL, 5%-15% of the cases) inheritance (Fahim et al. 2013). Unknown, simplex cases (single occurrence in a family) account for 40%-50%of cases and digenic inheritance has been reported (Fahim et al. 2013). To date, over 60 genes have been linked to nonsyndromic (~56 genes) and syndromic RP (RetNet; Daiger et al. 2013). It has been reported that it is now possible to detect disease-causing mutations in 56% of patients with adRP, roughly 30% of patients with recessive RP, and nearly 90% of patients with X-linked RP, which indicates that the there are several or many more RP genes that have yet to be discovered (Daiger et al. 2010).

The most common genes causing adRP are RHO (26-28% of all RP cases), PRPF31/RP11 (5-8%), PRPH2/RDS (4-8%), RP1 (6%), IMPDH1 (1-3%), KLHL7 (0.5-1.5%), NR2E3 (0.5-1.5%), PRPF3/RP18 (1%), PRPF8/RP13 (3%), CRX (1%) and TOPORS (1%) (Fahim et al. 2013; Daiger et al. 2010; Sullivan et al. 2013). The most common genes causing arRP are USH2A (10-15%), ABCA4 (2-5%), PDE6A (2-5%), PDE6B (2-5%), RPE65 (2-5%), and CNGA1 (1-2%). Considering only XLRP cases, pathogenic variants in RPGR account for the vast majority (~80%), with RP2 accounting for about 10% (Breuer et al. 2002; Sharon et al. 2003).

Among the RP genes, a few genes (BEST1, NR2E3, NRL, RDH12, RHO and RP1) have been reported to exhibit both ad and ar inheritance (Daiger et al. 2013).

The RP1 gene encodes a 2156 amino acid protein, which is localized in the connecting cilium and axoneme of photoreceptor sensory cilia. RP1 is a photoreceptor-specific microtubule-associated protein, which is essential for the correct localization and proper stacking of outer segment discs (Liu et al. 2003; Liu et al. 2004). Mutations in the RP1 gene account for ~5.5% adRP and ~1% of arRP cases (Chen et al. 2009). The inheritance mode is dependent on the type and position of the mutation (Siemiatkowska et al. 2012). Siemiatkowska et al. proposed that nonsense variants that occur in the “hot spot” region between amino acid residues 500-1053 of the RP1 protein act in a dominant negative manner to cause autosomal dominant RP. The missense variants that result in residual protein function and the protein-truncating variants near the 3′ end of the gene causes arRP (Siemiatkowska et al. 2012). Over 90 different RP1 pathogenic variants (missense, nonsense, small deletions, insertions and indels) have been reported (Human Gene Mutation Database).

Clinical Sensitivity - Sequencing with CNV PGxome

Mutations in the RP1 gene account for ~5.5% adRP and ~1% of arRP cases (Chen et al. 2009).

To date, there have been no reported gross deletions or duplications in RP1 (Human Gene Mutation Database).

Testing Strategy

This test provides full coverage of all coding exons of the RP1 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 autosomal dominant, autosomal recessive or sporadic RP. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in RP1.

Gene

Official Gene Symbol OMIM ID
RP1 603937
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Retinitis Pigmentosa 1 AR, AD 180100

Citations

  • Booij JC. et al. 2005. Journal of medical genetics. 42: e67. PubMed ID: 16272259
  • Breuer DK, Yashar BM, Filippova E, Hiriyanna S, Lyons RH, Mears AJ, Asaye B, Acar C, Vervoort R, Wright AF. 2002. A Comprehensive Mutation Analysis of RP2 and RPGR in a North American Cohort of Families with X-Linked Retinitis Pigmentosa. The American Journal of Human Genetics 70: 1545–1554. PubMed ID: 11992260
  • Chen LJ, Lai TYY, Tam POS, Chiang SWY, Zhang X, Lam S, Lai RYK, Lam DSC, Pang CP. 2010. Compound Heterozygosity of Two Novel Truncation Mutations in RP1 Causing Autosomal Recessive Retinitis Pigmentosa. Investigative Ophthalmology & Visual Science 51: 2236–2242. PubMed ID: 19933189
  • Daiger SP. et al. 2010. Advances in experimental medicine and biology. 664: 325-31. PubMed ID: 20238032
  • Daiger SP. et al. 2013. Clinical genetics. 84: 132-41. PubMed ID: 23701314
  • Fahim AT. et al. 2013. Retinitis Pigmentosa Overview. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews(®), Seattle (WA): University of Washington, Seattle. PubMed ID: 20301590
  • Human Gene Mutation Database (Bio-base).
  • Liu Q, Lyubarsky A, Skalet JH, Pugh EN, Pierce EA. 2003. RP1 is required for the correct stacking of outer segment discs. Investigative ophthalmology & visual science 44: 4171–4183. PubMed ID: 14507858
  • Liu Q, Zuo J, Pierce EA. 2004. The retinitis pigmentosa 1 protein is a photoreceptor microtubule-associated protein. The Journal of neuroscience 24: 6427–6436. PubMed ID: 15269252
  • RetNet: Genes and Mapped Loci Causing Retinal Diseases
  • Sharon D, Sandberg MA, Rabe VW, Stillberger M, Dryja TP, Berson EL. 2003. RP2 and RPGR Mutations and Clinical Correlations in Patients with X-Linked Retinitis Pigmentosa. The American Journal of Human Genetics 73: 1131–1146. PubMed ID: 14564670
  • Siemiatkowska AM, Astuti GD, Arimadyo K, Hollander AI den, Faradz SM, Cremers FP, Collin RW. 2012. Identification of a novel nonsense mutation in RP1 that causes autosomal recessive retinitis pigmentosa in an Indonesian family. Molecular vision 18: 2411. PubMed ID: 23077400
  • Sullivan LS. et al. 2013. Investigative ophthalmology & visual science. 54: 6255-61. PubMed ID: 23950152
  • Van Soest S., Westerveld A. 1999. Survey of ophthalmology. 43: 321-34. PubMed ID: 10025514

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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