DNA icon

Autosomal Recessive Retinitis Pigmentosa 26 (RP26) via the CERKL Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
6953 CERKL 81479 81479,81479 $990 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
6953CERKL81479 81479,81479 $990 Order Options and Pricing

Pricing Comments

This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

Testing run on PG-Select capture probes does not include exome-wide CNV analysis. Reflex is available to PGxome or an exome-based panel, or you can use this gene list to create a custom panel (click here).

Click here for costs to reflex to whole PGxome.

Turnaround Time

3 weeks on average for standard orders or 2 weeks 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 ("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). RP26 (OMIM # 608380) is characterized by equally affected cone and rod systems and pronounced macular atrophy (Avila-Fernandez et al. Invest Ophthalmol Vis Sci 49(6):2709-2713, 2008).

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). Ceramide kinase like protein, which is encoded by CERKL, is homologous to the Ceramide kinase protein (CERK: 29% identity; 50% similarity) (Sugiura et al. J Biol Chem 277(26):23294-23300, 2002), but does not have the same function as CERK (Bornancin et al. Biochim Biophys Acta 1687(1-3):31-43, 2005). In situ hybridization analysis on adult murine retina sections revealed that the CERKL protein is predominantly synthesized in the retinal ganglion cell layer and to a lesser extent in the inner nuclear and photoreceptor cell layers (Tuson et al. Am J Hum Genet 74(1):128-138, 2004). Ceramides are metabolites of the structural membrane component sphingolipid and have been implicated in apoptosis, growth suppression, and the stress response (Hannun et al. Science 274(5294):1855-1859, 1996). Tuson et al. (2004), linked RP to ceramide-induced apoptosis and suggested that the ceramide kinases convert ceramide into ceramide-1-phosphate and act as antiapoptotic and neuroprotective agents (Tuson et al., 2004). Kinase activity of CERKL is not yet proven (Bornancin et al., 2005). It has also been reported that CERKL contributes to nucleolar localization. Missense mutations in CERKL prevent the active transport of CERKL from the cytoplasm to the nucleolus. This would lead to the accumulation of CERKL in the cytoplasm that might induce apoptotic cell death and ultimately retinal degeneration (Ali et al. Mol Vis 14:1960-1964, 2008; Aleman et al. Invest Ophthalmol Vis Sci 50(12):5944-5954, 2009). So far, about 10 mutations (missense, nonsense, splicing, small insertions and deletions) have been associated with arRP26 (The Human Gene Mutation Database).

Clinical Sensitivity - Sequencing with CNV PG-Select

CERKL mutation screening in two hundred and ten unrelated Spanish families with nonsyndromic arRP identified a homozygous nonsense mutation (p.Arg257*) in all seven affected families (~3.3%) (Avila-Fernandez et al. Invest Ophthalmol Vis Sci 49(6):2709-2713, 2008). Another mutation analysis identified CERKL mutations in 2% of CRD cases (2/123), which were not present in 200 ethnically matched control alleles (Littink et al. Invest Ophthalmol Vis Sci 51(11):5943-5951, 2010). Another study identified CERKL mutations in two out of sixteen RP patients (~12.5%), which were not present in the control cohorts of 95 healthy North American or 95 Japanese individuals. All these mutations cosegregated with RP as recessive, pathogenic alleles in all family members (Nishiguchi et al Proc Natl Acad Sci USA 2013 Sep 16, Epub ahead of print). A prevalent CERKL founder mutation (c.238+1G>A) has been identified that underlies approximately 33% of autosomal recessive retinal degeneration cases in the Yemenite Jewish population (Auslender et al. Invest Ophthalmol Vis Sci 48(12):5431-5438, 2007).

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

Testing Strategy

This test provides full coverage of all coding exons of the CERKL gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

All patients with symptoms suggestive of arRP and arCRD, especially patients with pronounced macular atrophy, and relatives of patients with known CERKL mutations. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in CERKL.

Gene

Official Gene Symbol OMIM ID
CERKL 608381
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Retinitis Pigmentosa 26 608380

Related Tests

Name
Cone-Rod Dystrophy Panel
Retinitis Pigmentosa Panel

Citations

  • Aleman, T.S. et al. (2009). "CERKL mutations cause an autosomal recessive cone-rod dystrophy with inner retinopathy." Invest Ophthalmol Vis Sci 50(12):5944-5954. PubMed ID: 19578027
  • Ali, M. et al. (2008). "A missense mutation in the nuclear localization signal sequence of CERKL (p.R106S) causes autosomal recessive retinal degeneration." Mol Vis 14:1960-1964. PubMed ID: 18978954
  • Auslender, N. et al. (2007). "A common founder mutation of CERKL underlies autosomal recessive retinal degeneration with early macular involvement among Yemenite Jews." Invest Ophthalmol Vis Sci 48(12):5431-5438. PubMed ID: 18055789
  • Avila-Fernandez, A. et al. (2008). "CERKL mutations and associated phenotypes in seven Spanish families with autosomal recessive retinitis pigmentosa." Invest Ophthalmol Vis Sci 49(6):2709-2713. PubMed ID: 18515597
  • 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
  • Bornancin, F. et al.  (2005). "Characterization of a ceramide kinase-like protein." Biochim Biophys Acta 1687(1-3):31-43. PubMed ID: 15708351
  • Hannun, Y.A. et al. (1996). "Functions of ceramide in coordinating cellular responses to stress." Science 274(5294):1855-1859. PubMed ID: 8943189
  • Human Gene Mutation Database (Bio-base).
  • Littink, K.W. et al. (2010). "Homozygosity mapping in patients with cone-rod dystrophy: novel mutations and clinical characterizations." Invest Ophthalmol Vis Sci 51(11):5943-5951. PubMed ID: 20554613
  • Nishiguchi, K.M. et al. (2013). "Whole genome sequencing in patients with retinitis pigmentosa reveals pathogenic DNA structural changes and NEK2 as a new disease gene." Proc Natl Acad Sci USA [Epub ahead of print]. PubMed ID: 24043777
  • RetNet
  • Sugiura, M. et al. (2002). "Ceramide kinase, a novel lipid kinase. Molecular cloning and functional characterization." J Biol Chem 277(26):23294-23300, 2002. PubMed ID: 11956206
  • Tuson, M. et al. (2004). "Mutation of CERKL, a novel human ceramide kinase gene, causes autosomal recessive retinitis pigmentosa (RP26)." Am J Hum Genet 74(1):128-138. PubMed ID: 14681825
  • 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

loading Loading... ×

ORDER OPTIONS

An error has occurred while calculating the price. Please try again or contact us for assistance.

View Ordering Instructions

1) Select Test Method (Platform)


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: loading
Patient Prompt Pay Price: loading
A patient prompt pay discount is available if payment is made by the patient and received prior to the time of reporting.
Show Patient Prompt Pay Price
×
Copy Text to Clipboard
×