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Retinitis Pigmentosa 38 (RP38) via the MERTK 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
8049 MERTK 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8049MERTK81479 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) or rod cone dystrophies (RCDs) represent 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, followed by progressive degeneration of the photoreceptors, which eventually leads to blindness (van Soest et al. Surv Ophthalmol 43(4):321-334, 1999). In the early stages of disease, RP38 (OMIM # 613862) patients have distinct dot-like autofluorescent deposits in the fovea and macula (“bull's eye” pattern on funduscopy), which is a hallmark of RP38. Other salient features of RP38 are nyctalopia in early infancy, reduced visual acuity and decreased rod responses compared to cone at electroretinogram (Ksantini et al. Eur J Ophthalmol 22(4):647-653, 2012).

Genetics

Nonsyndromic RP is remarkably heterogeneous both clinically and genetically and exhibits autosomal dominant (ad), autosomal recessive (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 involved with adRP, arRP, and XLRP, respectively (RetNet). Mutations in MERTK cause arRP. MERTK (mer proto-oncogene tyrosine kinase; OMIM # 604705), which encodes a transmembrane receptor of tyrosine kinases, is predominantly expressed in retinal pigment epithelium (RPE), and monocytes/macrophages (Strick and Vollrath. Exp Eye Res 91(6):786-787, 2010). MERTK plays an essential role in triggering RPE-mediated phagocytosis for the regeneration/renewal of photoreceptor outer segments (OS) (Conlon et al. Hum Gene Ther Clin Dev 24(1):23-28, 2013). It has been reported in the Royal College of Surgeons (RCS) rat (a widely studied model for arRP) that mutations in MERTK impaired the RPE mediated phagocytic activity and resulted in accumulation of OS debris in the interphotoreceptor space and ultimately lead to retinal degeneration (Gal et al. Nat Genet 26(3):270-271, 2000). MERTK gene replacement therapy using different viral vectors was shown to be effective and safe in the RCS rat (Conlon et al., 2013; D'Cruz et al. Hum Mol Genet 9(4):645-651, 2000). There are about 30 causative mutations reported in MERTK, which include missense mutations, small insertions and deletions (Human Gene Mutation Database).

Clinical Sensitivity - Sequencing with CNV PGxome

MERTK mutation screening in a cohort of 328 probands with various retinal dystrophies identified three mutations in three individuals with RP (Gal et al. Nat Genet 26(3):270-271, 2000). A different study showed that MERTK mutations account for about 1% (1/96) of non-syndromic arRP cases (Tschernutter et al. Br J Ophthalmol 90(6):718-723, 2006).

So far, three gross deletions have been reported in MERTK (Human Gene Mutation Database). A gross deletion of exons 1–7 of MERTK is a common founder mutation in the Faroe Islands in Denmark and accounts for ~30% (7/25) of non-syndromic of RP cases in this population (Ostergaard et al. Mol Vis 17:1485-1492, 2011).

Testing Strategy

This test provides full coverage of all coding exons of the MERTK 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 arRP, especially patients with distinct dot-like autofluorescent deposits in fovea and macula (“bull's eye” pattern on funduscopy). This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in MERTK.

Gene

Official Gene Symbol OMIM ID
MERTK 604705
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Retinitis Pigmentosa 38 AR 613862

Related Tests

Name
Leber Congenital Amaurosis Panel
Retinitis Pigmentosa (includes RPGR ORF15) Panel

Citations

  • 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
  • Conlon, T.J. et al. (2013). "Preclinical potency and safety studies of an AAV2-mediated gene therapy vector for the treatment of MERTK associated retinitis pigmentosa." Hum Gene Ther Clin Dev 24(1):23-28. PubMed ID: 23692380
  • D'Cruz, P.M. et al. (2000). "Mutation of the receptor tyrosine kinase gene Mertk in the retinal dystrophic RCS rat." Hum Mol Genet 9(4):645-651. PubMed ID: 10699188
  • Gal, A. et al. (2000). "Mutations in MERTK, the human orthologue of the RCS rat retinal dystrophy gene, cause retinitis pigmentosa." Nat Genet 26(3):270-271. PubMed ID: 11062461
  • Human Gene Mutation Database (Bio-base).
  • Ksantini, M. et al. "Homozygous mutation in MERTK causes severe autosomal recessive retinitis pigmentosa." Eur J Ophthalmol 22(4):647-653, 2012. PubMed ID: 22180149
  • Ostergaard, E., et al. (2011). "A novel MERTK deletion is a common founder mutation in the Faroe Islands and is responsible for a high proportion of retinitis pigmentosa cases." Mol Vis 17:1485-1492. PubMed ID: 21677792
  • RetNet: Genes and Mapped Loci Causing Retinal Diseases
  • Strick, D.J. and Vollrath, D. (2010).  "Focus on molecules: MERTK." Exp Eye Res 91(6):786-787. PubMed ID: 20488176
  • Tschernutter, M. et al. (2006). "Clinical characterisation of a family with retinal dystrophy caused by mutation in the Mertk gene."  Br J Ophthalmol 90(6):718-723. PubMed ID: 16714263
  • 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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