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Fish-Eye Disease and Norum Disease via the LCAT 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
8651 LCAT 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8651LCAT81479 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

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

Fish eye disease (FED) is due to the deficiency of plasma lecithin-cholesterol acyltransferase (alpha-LCAT deficiency) and is referred to as incomplete or partial LCAT deficiency. FED is characterized by severe corneal opacities due to abnormal corneal lipid deposition, causing impaired vision which eventually leads to blindness. Other symptoms include dyslipoproteinaemia, which is characterized by increased levels of very low and low density lipoproteins (VLDL and LDL) and a 90% reduction in the level of high-density lipoprotein (HDL) (Carlson 1982; Carlson and Philipson 1979).

Clinically, FED differs from other familial conditions with deficiency of HDL such as Tangier disease, Milano-AI-apoprotein disease, and familial LCAT-deficiency (FLD) (due to alpha- and beta-LCAT deficiency referred as complete LCAT deficiency, also known as Norum disease). FLD is a severe form of disease and apart from corneal opacification patients present with normochromic anemia and progressive renal failure (by 4th to 5th decade) (Carlson 1982).

Genetics

FED and FLD are autosomal recessive disorders. Both are due to homozygous or compound heterozygous pathogenic variants in LCAT (Holleboom et al. 2011). Missense variants dispersed in different regions of the LCAT gene were reported in both FLD and FED cases, which suggests several functionally important structural domains (Funke et al. 1993). Looking at the documented pathogenic variants in the Human Gene Mutation Database, protein truncating variants were reported in only FLD cases (HGMD). No other genotype-pyhentype correlations have been reported. LCAT pathogenic variants were highly prevalent in patients with low HDL cholesterol levels in the Netherlands due to the founder mutation p.Thr147Ile (Holleboom et al. 2011). So far, over 100 pathogenic variants (missense, nonsense, splicing, small and gross deletions and duplications and small indels) have been reported in LCAT (HGMD).

LCAT encodes a highly conserved enzyme lecithin:cholesterol acyltransferase (LCAT) that catalyzes the formation of most plasma cholesterol ester and plays an important role in the reverse transport of cholesterol from peripheral tissue to the liver (Maeda et al. 1991).

Clinical Sensitivity - Sequencing with CNV PGxome

A mutation screening in Netherlands patients with low HDL levels identified LCAT pathogenic variants in 29% (28 of the 98) of patients and 18 of them carried the same variant (p.Thr147Ile), suggesting that it is a founder mutation (Holleboom et al. 2011).

Testing Strategy

This test provides full coverage of all coding exons of the LCAT 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 Fish eye disease and familial LCAT-deficiency patients and all patients with high density lipoprotein deficiency are candidates. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in LCAT.

Gene

Official Gene Symbol OMIM ID
LCAT 606967
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Diseases

Name Inheritance OMIM ID
Fish-Eye Disease AR 136120
Norum Disease AR 245900

Citations

  • Carlson LA. 1982. European journal of clinical investigation. 12: 41-53. PubMed ID: 6802651
  • Carlson LA., Philipson B. 1979. Lancet (London, England). 2: 922-4. PubMed ID: 91022
  • Funke H. et al. 1993. The Journal of clinical investigation. 91: 677-83. PubMed ID: 8432868
  • Holleboom AG. et al. 2011. Human mutation. 32: 1290-8. PubMed ID: 21901787
  • Human Gene Mutation Database (Bio-base).
  • Maeda E. et al. 1991. Biochemical and biophysical research communications. 178: 460-6. PubMed ID: 1859405

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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