Leber Congenital Amaurosis 10 (LCA10) via the CEP290 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
4367 CEP290 81408 81408,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
4367CEP29081408 81408(x1), 81479(x1) $640 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.

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

Leber congenital amaurosis (LCA, OMIM# 204000) is the most severe form of inherited retinal dystrophy that is usually evident at birth or during the first months of life. LCA is clinically characterized by poor visual function often accompanied by sensory nystagmus, abnormal pupillary responses, high hyperopia, severely reduced visual acuity, photo-aversion, markedly diminished electroretinogram (ERG) and keratoconus condition due to oculo-digital signs of Franceschetti such as eye poking, pressing, and rubbing the eyes with a knuckle or finger (Weleber et al. GeneReviews, 2013). The estimated prevalence of LCA is 2-3 per 100,000 live births and accounts for 10-18% of congenital blindness (Fazzi et al. Eur J Paediatr Neurol 7(1):13-22, 2003).

Genetics

LCA is a genetically heterogeneous disorder and is often inherited in an autosomal recessive manner. To date, approximately 19 genes have been implicated in the pathogenesis of different types of LCA (Weleber et al., 2013; Chen et al. Invest Ophthalmol Vis Sci 54(6):4351-4357, 2013). Together these genes account for 70% of the LCA cases. These genes encode proteins that have a wide range of retinal functions, such as photoreceptor morphogenesis, phototransduction, vitamin A cycling, guanine synthesis, and outer segment phagocytosis (den Hollander et al. Prog Retin Eye Res 27(4):391-419, 2008). Mutations in these genes cause not only LCA but also other retinal disorders (Weleber. Ophthalmic Genet 23(2):71-97, 2002). To date, mutations in CEP290 (also known as NPHP6, OMIM 610142) are the most frequent cause of LCA and are referred to as LCA10 (OMIM 611755) (den Hollander et al. Am J Hum Genet 79(3):556-561, 2006). CEP290, which is located on Chromosome 12, encodes a centrosomal protein that localizes primarily to centrosomes of dividing cells and to the connecting ciliated cells of inner and outer segments of the retinal photoreceptors (Chang et al. Hum Mol Genet 15(11):1847-1857, 2006). Perturbations in the photoreceptor ciliary transports due to mutations in CEP290 are associated with retinal degeneration as well as more pleiotropic phenotypes that include Joubert syndrome, Bardet-Biedl syndrome, lethal Meckel-Grüber syndrome (MKS), etc. (Adams et al. Ophthalmic Genet 28:113-125, 2007; Coppieters et al. Hum Mutat 31(10):E1709-1766, 2010; Yzer et al. Molecular Vision 18:412-425, 2012). Over 70 mutations in CEP290 account for ~21% of the LCA cases and two-thirds of all mutant alleles carry the intronic mutation c.2991+1655A>G. This mutation creates a strong splice donor site that leads to insertion of a cryptic exon encoding a premature stop codon (p.Cys998X). Genes with this mutation appear to produce a small amount of residual protein, which might be sufficient for normal cerebellar and renal function but not for the proper function of the photoreceptors and therefore leads specifically to the retinal degeneration (den Hollander et al., 2006).

Clinical Sensitivity - Sequencing with CNV PG-Select

A study identified the c.2991+1655A>G CEP290 mutation in 21% (16/76 of LCA patients; 62.5% of all mutant alleles) of unrelated patients with LCA, either homozygously or compound heterozygously and reported it as the major LCA-associated gene of European ancestry (den Hollander et al. Am J Hum Genet 79(3): 556-561, 2006). The Perrault et al (2007) study also reported the high frequency of CEP290 mutations in their LCA cohort (22%; 21/96) and suggested that CEP290 is involved in families of European descent only (38/38) (Perrault et al. Hum Mutat 28(4):416, 2007). However, they reported 23 novel mutations and only 43% (33/76) of mutant alleles had c.2991+1655A>G mutations. Moreover, 12 families did not carry this common intronic causative mutation.

To date, no gross deletions have been reported in CEP290 that are associated with Leber congenital amaurosis 10 (The Human Gene Mutation Database).

Testing Strategy

This test provides full coverage of all coding exons of the CEP290 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

Candidates for this test are all LCA patients, patients with symptoms consistent with LCA10, family members of patients who have known mutations and carrier testing for at-risk family members.

Gene

Official Gene Symbol OMIM ID
CEP290 610142
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Tests

Name
Joubert and Meckel-Gruber Syndromes via the CEP290 Gene
Leber Congenital Amaurosis Panel
Nephronophthisis and Senior-Loken Syndrome Panel
Retinitis Pigmentosa (includes RPGR ORF15) Panel

Citations

  • Adams, N.A. et al. (2007).  PubMed ID: 17896309
  • Chang, B. et al. (2006). PubMed ID: 16632484
  • Chen, Y. et al. (2013). PubMed ID: 23661368
  • Coppieters, F. et al. (2010).  PubMed ID: 20683928
  • den Hollander AI, Roepman R, Koenekoop RK, Cremers FPM. 2008. Leber congenital amaurosis: genes, proteins and disease mechanisms. Prog Retin Eye Res 27: 391–419. PubMed ID: 18632300
  • den Hollander, A.I. et al. (2006).  PubMed ID: 16909394
  • Fazzi E, Signorini SG, Scelsa B, Bova SM, Lanzi G. 2003. Leber’s congenital amaurosis: an update. Eur. J. Paediatr. Neurol. 7: 13–22. PubMed ID: 12615170
  • Human Gene Mutation Database (Bio-base).
  • Perrault, I. et.al. (2007). PubMed ID: 17345604
  • Weleber RG, Francis PJ, Trzupek KM, Beattie C. 2013. Leber Congenital Amaurosis. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong C-T, and Stephens K, editors. GeneReviews™, Seattle (WA): University of Washington, Seattle. PubMed ID: 20301475
  • Weleber RG. 2002. Infantile and childhood retinal blindness: a molecular perspective (The Franceschetti Lecture). Ophthalmic Genet. 23: 71–97. PubMed ID: 12187427
  • Yzer, S. et al. (2012).  PubMed ID: 22355252

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

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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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