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Autosomal Dominant Retinitis Pigmentosa 27 (RP27) and Autosomal Recessive Retinal Degeneration, Clumped Pigment Type via the NRL 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
9067 NRL 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9067NRL81479 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

Retinitis pigmentosa (RP; OMIM # 268000) represents a group of hereditary retinal dystrophies with a worldwide prevalence of ~1 in 4000 (Booij et al. J Med Genet 42 (11): e67, 2005). RP is clinically characterized by retinal pigment deposits visible on fundus examination, nyctalopia ("night blindness"), followed by progressive degeneration of the photoreceptors, which eventually leads to blindness (van Soest et al. Surv Ophthalmol 43(4):321-334, 1999).

The hallmark of autosomal recessive (ar) retinal degeneration, clumped pigment type is abnormal pigment clumping in the periphery, which is is found in ~0.5% of RP cases (Nishiguchi et al. Proc Natl Acad Sci USA 101(51):17819-17824, 2004). Autosomal dominant (ad) RP27 (OMIM # 613750) affected patients did not show clumped pigment deposits. The characteristic features of RP27 are early onset of nyctalopia (birth - 16 years of age), and abnormal peripheral vision with a mild reduction in visual acuity seen in the 2nd and 3rd decades of life. As the disease progresses, a substantial loss of visual acuity associated with distinctive peripapillary chorioretinal atrophy develops. It has been observed that all the components of electroretinogram are nondetectable in older individuals (Bessant et al. Arch Ophthalmol 121(6):793-802, 2003; Nishiguchi et al., 2004).

Genetics

Nonsyndromic RP is remarkably heterogeneous both clinically and genetically and exhibits ad, ar or X-linked (XL) inheritance. To date, over 50 loci have been linked to nonsyndromic RP and 18, 27 and 2 genes have been identified that are associated with adRP, arRP, and XLRP, respectively (RetNet). The neural retina leucine zipper gene (NRL; OMIM # 162080) on chromosome 14q11.2, which encodes an evolutionarily conserved basic motif-leucine zipper (bZIP) transcription factor is preferentially expressed in rod photoreceptors. NRL is shown to regulate the rod photoreceptor differentiation during mammalian retinal development and also interacts with CRX (cone-rod homeobox), NR2E3 (Retina-Specific Nuclear Receptor), and other transcription factors and synergistically regulates the activity of phototransduction genes (Mears et al. Nat Genet 29(4):447-452, 2001). Kanda et al. (2007) reported that gain-of-function mutations in the NRL gene cause adRP while loss-of-function NRL mutations lead to arRP (Kanda et al. Hum Mutat 28(6):589-598, 2007). So far, missense mutations, small deletions and insertions have been reported in NRL (The Human Gene Mutation Database). It has also been reported that causative mutations in NRL alter NRL phosphorylation and consequently its function and perturb gene expression in rods, resulting in photoreceptor degeneration in retinopathies (Swain et al. Mol Vis 13:1114-1120, 2007).

Clinical Sensitivity - Sequencing with CNV PGxome

Mutational screening in 519 adRP patients from North America, England and Spain, identified NRL mutations in 8 patients (~1.5%) which were not found in 9 control subjects (DeAngelis et al. Arch Ophthalmol 120(3):369-375, 2002). In another mutational screening in 167 adRP Spanish patients, four patients (~2%) had NRL mutations (Martinez-Gimeno et al. Hum Mutat 17(6):520, 2001).

So far, no gross deletions or duplications have been reported in NRL (Human Gene Mutation Database).

Testing Strategy

This test provides full coverage of all coding exons of the NRL 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 adRP and arRP, especially patients with an unusual pigment clumping in the periphery and patients with symptoms suggestive of RP27 described in the clinical features section. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in NRL.

Gene

Official Gene Symbol OMIM ID
NRL 162080
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Retinitis Pigmentosa 27 AD 613750

Related Test

Name
Retinitis Pigmentosa (includes RPGR ORF15) Panel

Citations

  • Bessant, D.A. et al. (2003). "Phenotype of retinitis pigmentosa associated with the Ser50Thr mutation in the NRL gene." Arch Ophthalmol 121(6):793-802. PubMed ID: 12796249
  • Booij JC. 2005. Identification of mutations in the AIPL1, CRB1, GUCY2D, RPE65, and RPGRIP1 genes in patients with juvenile retinitis pigmentosa. Journal of Medical Genetics 42: e67–e67. PubMed ID: 16272259
  • DeAngelis, M.M. et al. (2002). "Novel mutations in the NRL gene and associated clinical findings in patients with dominant retinitis pigmentosa." Arch Ophthalmol 120(3):369-375. PubMed ID: 11879142
  • Human Gene Mutation Database (Bio-base).
  • Kanda, A. et al. (2007). "Retinopathy mutations in the bZIP protein NRL alter phosphorylation and transcriptional activity." Hum Mutat 28(6):589-598. PubMed ID: 17335001
  • Martinez-Gimeno, M. et al. (2001). "Mutations P51U and G122E in retinal transcription factor NRL associated with autosomal dominant and sporadic retinitis pigmentosa." Hum Mutat 17(6):520. PubMed ID: 11385710
  • Mears, A.J. et al. (2001). "Nrl is required for rod photoreceptor development." Nat Genet 29(4):447-452. PubMed ID: 11694879
  • Nishiguchi, K.M. et al. (2004). "Recessive NRL mutations in patients with clumped pigmentary retinal degeneration and relative preservation of blue cone function." Proc Natl Acad Sci USA 101(51):17819-17824. PubMed ID: 15591106
  • RetNet
  • Swain, P. et al. (2007). "Mutations associated with retinopathies alter mitogen-activated protein kinase-induced phosphorylation of neural retina leucine-zipper." Mol Vis 13:1114-1120. PubMed ID: 17653056
  • 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.
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