Leber Congenital Amaurosis 14 (LCA14) or Early Onset Retinal Dystrophy (EORD) and Juvenile Retinitis Pigmentosa via the LRAT 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
9191 LRAT 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9191LRAT81479 81479(x2) $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

Clinical Features and Genetics

Clinical Features

Leber congenital amaurosis 14 (LCA14; OMIM 613341), also known as Early Onset Retinal Dystrophy (EORD), is a severe form of retinal disease that typically becomes evident in the first year of life (Weleber et al. GeneReviews, 2013), whereas the less severe forms are usually considered juvenile retinitis pigmentosa (Gu et al. Nature Genetics 17: 194 -197, 1997). EORD is typically characterized by poor visual function often accompanied by nystagmus (involuntary movement of eye ball), sluggish or absent pupillary responses, severe vision loss or nyctalopia (night blindness), photoaversion, high hyperopia (far-sightedness) and severely attenuated rod and cone responses on full-field electroretinography (ERG). Additionally, EORD affected individuals present with a special behavior called Franceschetti's oculo-digital signs like eye poking, pressing, and rubbing the eyes with a knuckle or finger that may contribute to deep-set eyes and keratoconus condition (cone-shaped and abnormally thin cornea) (Weleber et al., 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 clinically and genetically heterogenous 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. GeneReviews, 2013; Chen Y et al. Invest Ophthalmol Vis Sci, 2013). LCA14/EORD is caused by causative mutations in the LRAT gene located on chromosome 4q31. LRAT encodes the Lecithin-retinol acyltransferase enzyme present mainly in the retinal pigment epithelium (RPE) and liver. LRAT, RPE-Specific Protein 65 (RPE65) and Retinol dehydrogenase 12 (RDH12)  are responsible for vitamin A metabolism in the visual cycle to synthesize 11-cis-retinaldehyde, a chromophore of all known visual pigments (Ruiz et al. Invest Ophthalmol Vis Sci 42(1):31-7, 2001). Phenotype-genotype analysis shows high penetrance of LCA. However, the phenotypic variations among patients with the same mutation indicates the influence of genetic background, environment and other factors (Li et al. Invest Ophthalmol Vis Sci  50(3):1336-43, 2009). LRAT, RPE65 and RDH12 mutations lead to similar phenotypes, suggesting the need to screen these genes systematically (Sénéchal et al. Am J Ophthalmol 142(4):702-4, 2006). Mutations in these three genes account for ~10% of LCA patients.

Clinical Sensitivity - Sequencing with CNV PGxome

Dev Borman, A. et al (2012) suggested that the frequency of LRAT mutations in LCA14 and EORD patients is about 1%, which is consistent with previous studies and confirms that LRAT mutations are a rare cause of LCA and EORD (Dev Borman, A., et al. Invest Ophthalmol Vis Sci 53(7):3927-3938, 2012).

No gross deletions or gross insertion/duplications have been reported in LRAT (Human Gene Mutation Database).

Testing Strategy

This test provides full coverage of all coding exons of the LRAT 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

Candidates for this test are patients with symptoms consistent with LCA14 or EORD and Juvenile Retinitis pigmentosa, family members of patients who have known mutations and carrier testing for at-risk family members. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in LRAT.

Gene

Official Gene Symbol OMIM ID
LRAT 604863
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Leber Congenital Amaurosis 14 AR 613341

Related Tests

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

Citations

  • Chen Y, Zhang Q, Shen T, Xiao X, Li S, Guan L, Zhang J, Zhu Z, Yin Y, Wang P, Guo X, Wang J, et al. 2013. Comprehensive Mutation Analysis by Whole-Exome Sequencing in 41 Chinese Families With Leber Congenital Amaurosis. Investigative Ophthalmology & Visual Science 54: 4351–4357. PubMed ID: 23661368
  • Dev Borman A et al. (2012). Early onset retinal dystrophy due to mutations in LRAT: molecular analysis and detailed phenotypic study." Invest Ophthalmol Vis Sci 53(7):3927-3938. PubMed ID: 22570351
  • 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
  • Gu, S. M., et.al. (1997). "Mutations in RPE65 cause autosomal recessive childhood-onset severe retinal dystrophy." Nat Genet 17(2): 194-7. PubMed ID: 9326941
  • Human Gene Mutation Database (Bio-base).
  • Li Y et al. (2009). "Mutation survey of known LCA genes and loci in the Saudi Arabian population." Invest Ophthalmol Vis Sci 50(3):1336-43. PubMed ID: 18936139
  • Ruiz A et al. (2001). "Genomic organization and mutation analysis of the gene encoding lecithin retinol acyltransferase in human retinal pigment epithelium." Invest Ophthalmol Vis Sci  42(1):31-7. PubMed ID: 11133845
  • Sénéchal A, et al. (2006). "Screening genes of the retinoid metabolism: novel LRAT mutation in leber congenital amaurosis." Am J Ophthalmol 142(4):702-4. PubMed ID: 17011878
  • 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

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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