X-linked Retinitis Pigmentosa (XLRP) via the RPGR (includes ORF15) 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
11013 RPGR 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11013RPGR81479 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.

A 25% additional charge will be applied to STAT orders. View STAT turnaround times here.

For Reflex to PGxome pricing click here.

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

For Sanger Sequencing click here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

Turnaround Time

18 days on average

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

Retinitis pigmentosa (RP) refers to a group of related eye disorders stemming from the degeneration of photoreceptor cells in the retina (Pagon and Daiger, 2005). RP derives its name from retinal pigmentation changes. In RP patients, pigment granules accumulate in perivascular clusters, called bone-spicules, in the retinal pigment epithelium (RPE). The accumulation of pigment is typically accompanied by death of the photoreceptor cells, first rods and eventually cones. As a result, RP will often present first with night blindness and decreased peripheral vision due to systematic loss of rod cells, followed by deterioration of central vision acuity and day blindness from the loss of cone cells. RP has an incidence of ~1/3500 and can be inherited in autosomal recessive, autosomal dominant, X-linked, digenic, and even mitochondrial patterns. Currently, variants in over 30 genes are known to cause RP.

Genetics

X-linked RP (XLRP) is one of the most severe forms of RP, with early onset and rapid progression in males. Milder symptoms can also present in females, probably due to random X inactivation. At least five different genetic loci have been associated with XLRP: Xp11.2 (RP2), Xp21.1 (RPGR), Xp21.2-21.3 (RP6), Xp22 (RP23), and Xp26-27 (RP24) (http://www.sph.uth.tmc.edu/RetNet/disease.htm). To date, only the RP2 and RPGR genes have been identified. RPGR encodes the retinitis pigmentosa GTPase regulator (Meindl et al. 1996), and RP2 encodes a protein of unknown function. Variants in RPGR account for the vast majority (~80%) of all XLRP cases, with RP2 accounting for about 10% of cases and the other loci likely accounting for the remainder (~10%) (Breuer et al. 2002; Sharon et al. 2003). Males hemizygous for RPGR variants typically display classic features of RP, such as initial night blindness and loss of peripheral vision. However, RPGR variants have also been detected in patients presenting with cone dystrophy (Yang et al. 2002; Demirci et al. 2002) or atrophic macular degeneration (Ayyagari et al. 2002). The RPGR gene encodes several alternatively spliced isoforms, although RP-causing variants are only found in isoform C (CCDS35229.1). Isoform C consists of 15 coding exons, with exon 15 (usually referred to as ORF15; see Bader et al. 2003 for a detailed description of ORF15) coding for nearly 50% of the protein. Accordingly, variants in ORF15 account for ~50% of all XLRP cases (Vervoort et al. 2000; Sharon et al. 2003).

Clinical Sensitivity - Sequencing with CNV PGxome

This test is predicted to detect a causative variant in ~70-80% of all patients with presumptive XLRP (Sharon et al. Am J Hum Genet 73:1131-1146, 2003; Hong et al. Invest Ophthalmol Vis Sci 46:435-441, 2005) or ~45% of patients with X-linked cone dystrophy (Demirci et al. Am J Hum Genet 70:1049-1053, 2002). The sensitivity for X-linked atrophic macular degeneration is unknown.

Testing Strategy

This test provides full coverage of all coding exons of the RPGR 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.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Targeted testing strategy for exons 1 to 14 For exons through 1 to 14, we will also sequence any single exon (Test #100) or pair of exons (Test #200) in family members of patients with known variants or to confirm research results.

Targeted testing strategy for exon 15 (ORF15) We will sequence ORF15 (Test #2085, $440) for clients who want to test this entire region.

Indications for Test

This test is for patients with probable X-linked recessive retinitis pigmentosa (XLRP), cone dystrophy (COD1) or atrophic macular degeneration.

Gene

Official Gene Symbol OMIM ID
RPGR 312610
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Tests

Name
RLBP1-Related Disorders via the RLBP1 Gene
Primary Ciliary Dyskinesia (PCD) via the RPGR Gene
Retinitis Pigmentosa (includes RPGR ORF15) Panel
Specialized Sequencing of the Mutational Hotspot RPGR (isoform C) ORF15 Region

Citations

  • Ayyagari R, Demirci FY, Liu J, Bingham EL, Stringham H, Kakuk LE, Boehnke M, Gorin MB, Richards JE, Sieving PA. 2002. X-linked recessive atrophic macular degeneration from RPGR mutation. Genomics 80: 166–171. PubMed ID: 12160730
  • Demirci FYK, Rigatti BW, Wen G, Radak AL, Mah TS, Baic CL, Traboulsi EI, Alitalo T, Ramser J, Gorin MB. 2002. X-Linked Cone-Rod Dystrophy (Locus< i> COD1): Identification of Mutations in RPGR Exon ORF15. The American Journal of Human Genetics 70: 1049–1053. PubMed ID: 11857109
  • 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
  • Hong D-H. 2005. A Single, Abbreviated RPGR-ORF15 Variant Reconstitutes RPGR Function In Vivo. Investigative Ophthalmology & Visual Science 46: 435–441. PubMed ID: 15671266
  • Meindl A, Dry K, Herrmann K, Manson F, Ciccodicola A, Edgar A, Carvalho MR, Achatz H, Hellebrand H, Lennon A, Migliaccio C, Porter K, et al. 1996. A gene (RPGR) with homology to the RCC1 guanine nucleotide exchange factor is mutated in X-linked retinitis pigmentosa (RP3). Nat. Genet. 13: 35–42. PubMed ID: 8673101
  • 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
  • Vervoort R, Lennon A, Bird AC, Tulloch B, Axton R, Miano MG, Meindl A, Meitinger T, Ciccodicola A, Wright AF. 2000. Mutational hot spot within a new RPGR exon in X-linked retinitis pigmentosa. Nature genetics 25: 462–466. PubMed ID: 10932196
  • Yang Z, Peachey NS, Moshfeghi DM, Thirumalaichary S, Chorich L, Shugart YY, Fan K, Zhang K. 2002. Mutations in the RPGR gene cause X-linked cone dystrophy. Hum. Mol. Genet. 11: 605–611. PubMed ID: 11875055

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

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