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Leber Congenital Amaurosis- 5 via the LCA5 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
7727 LCA5 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
7727LCA581479 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.

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

Leber congenital amaurosis (LCA) is a severe form of inherited retinal degeneration that is usually evident at birth or during the first months of life. LCA is clinically characterized by poor visual function often accompanied by nystagmus, abnormal pupillary responses, photophobia, high hyperopia, markedly diminished electroretinogram (ERG) and keratoconus due to oculo-digital signs of Franceschetti such as eye poking, pressing, and rubbing the eyes with a knuckle or finger (Weleber et al. 1993. PubMed ID: 20301475; Perrault et al. 1996. PubMed ID: 8944027). The estimated prevalence of LCA is 2-3 per 100,000 live births and accounts for 10-18% of congenital blindness (Fazzi et al. 2003. PubMed ID: 12615170).

With the advent of gene therapy and other types of treatments, the identification of causative genes and variants is becoming increasingly important.

Genetics

LCA is a genetically heterogeneous disorder and is often inherited in an autosomal recessive manner. To date, over 20 genes have been implicated in the pathogenesis of different types of LCA (Weleber et al. 1993. PubMed ID: 20301475; Chen et al. 2013. PubMed ID: 23661368). Together these genes account for 70-75% of the LCA cases (Wang et al. 2015. PubMed ID: 26047050; den Hollander et al. 2008. PubMed ID: 18632300). 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. 2008. PubMed ID: 18632300). Pathogenic variants in these genes cause not only LCA, but also other retinal disorders such as retinitis pigmentosa (Weleber. 2002. PubMed ID: 12187427; Wang et al. 2015. PubMed ID: 26047050; Wang et al. 2013. PubMed ID: 23847139; http://www.omim.org/; Human Gene Mutation Database).

Pathogenic variants in LCA5 are associated with a severe autosomal recessive form of LCA (Gerber et al. 2007. PubMed ID: 18000884) and also a few cases of Retinitis pigmentosa (Mackay et al. 2013. PubMed ID: 23946133). LCA5 encodes lebercilin protein, which is uniquely localized to connecting cilia that bridges the inner and outer segments of photoreceptor cells. Lebercilin has been shown to physically interact with IFT complex. Mouse model studies demonstrated that Lca5 inactivation resulted in perturbed molecular interconnectivity between lebercilin and the intraflagellar transport (IFT) machinery, which may affect ciliary trafficking and its associated protein transport in photoreceptors, leading to degeneration (Boldt et al. 2011. PubMed ID: 21606596).

Over 50 different LCA5 variants have been documented to be causative. They include missense, nonsense, splicing, and small deletions, indels and insertions and copy number variants. To date, no de novo pathogenic variants have been documented (Human Gene Mutation Database).

Clinical Sensitivity - Sequencing with CNV PGxome

Clinical sensitivity for LCA5 is reported to be 1-2% (Weleber et al. 1993. PubMed ID: 20301475; Gerber et al. 2007. PubMed ID: 18000884). Copy number variants have been reported in LCA5 (Human Gene Mutation Database).

Testing Strategy

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This test provides full coverage of all coding exons of the LCA5 gene plus 10 bases flanking noncoding DNA in all available transcripts in addition to 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

Candidates for this test are all Leber congenital amaurosis patients. Carrier testing is available for individuals with a family history of the disease and for the reproductive partners of individuals who carry pathogenic variants in LCA5.

Gene

Official Gene Symbol OMIM ID
LCA5 611408
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Leber Congenital Amaurosis 5 AR 604537

Citations

  • Boldt et al. 2011. PubMed ID: 21606596
  • Chen et al. 2013. PubMed ID: 23661368
  • den Hollander et al. 2008. PubMed ID: 18632300
  • Fazzi et al. 2003. PubMed ID: 12615170
  • Gerber et al. 2007. PubMed ID: 18000884
  • Human Gene Mutation Database (Bio-base).
  • Mackay et al. 2013. PubMed ID: 23946133
  • Online Mendelian Inheritance Man (OMIM).
  • Perrault et al. 1996. PubMed ID: 8944027
  • Wang et al. 2013. PubMed ID: 23847139
  • Wang et al. 2015. PubMed ID: 26047050
  • Weleber et al. 1993. PubMed ID: 20301475
  • Weleber. 2002. PubMed ID: 12187427

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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