Autosomal Dominant Stargardt disease (STGD3) via the ELOVL4 Gene
Summary and Pricing 
Test Method
Exome Sequencing with CNV Detection
| Test Code | Test Copy Genes | Test CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
|---|---|---|---|---|---|
| 8715 | ELOVL4 | 81479 | 81479,81479 | $990 | 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 platform).
Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing platform).
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.
Clinical Features and Genetics
Clinical Features
Stargardt disease (STGD) is a juvenile onset form of macular dystrophy/degeneration (MD) characterized by loss of photoreceptor cells in the macula, resulting in a severe reduction of central vision with a variable phenotype and a variable age of onset and severity. STGD is considered one of the most frequent causes of MD in childhood, accounting for approximately 7% of all retinal degenerative diseases (RDDs) with an estimated prevalence of 1 in 10,000 and a carrier frequency of 2% (Shastry 2008). Clinical features include progressive bilateral degeneration of the macula and retinal pigment epithelium (RPE) with characteristic orange-yellow flecks located around the macula or the mid peripheral retina (Rossi et al. 2012). The hallmark of STGD is massive accumulation of cellular debris, presumably lipofuscin in the RPE (usually seen in normal aging human eyes) (Fishman et al. 1987), which is clinically similar to fundus flavimaculatus (FFM) that has a later age of onset (20-64 years) and slower progression or milder visual loss compared to STGD (Kaplan et al. 1993). Genetic analysis suggests that STGD and FFM are allelic disorders with slightly different clinical manifestations (Shastry 2008).
ELOVL4-associated STGD (STGD3) is clinically similar to STGD, with the exception of the pattern of inheritance (Stone et al. 1994).
Genetics
STGD is usually inherited in an autosomal recessive (ar) manner and, less commonly, as an autosomal dominant (ad) trait (Rossi et al. 2012). The common STGD form is caused by recessive mutations in the ABCA4 gene and the rare ad form STGD3 is due to mutations in the ELOVL4 gene (Vasireddy et al. 2010). A ELOVL4 mutational screening a large independent pedigree affected by an autosomal dominant macular dystrophy detected an ELOVL4 mutation in all affected members, which was absent in in healthy control individuals (Bernstein et al. 2001). Another study in two adSTGD affected patients detected an ELOVL4 mutation in both, which was absent in in 96 healthy control individuals (Maugeri 2004). ELOVL4, which is located on chromosome 6, is predicted to encode an enzyme involved in the elongation of very long-chain fatty acids (ELOVL). This enzyme is highly expressed in photoreceptor cells. Mouse mutant studies suggested that the mutations in ELOVL4 leads to photoreceptor degeneration (Karan et al. 2005). So far, about 5 mutations (Missense/nonsense, small deletions and small indels) have been reported in ELOVL4 that are involved in the STGD phenotype (Human Gene Mutation Database).
Clinical Sensitivity - Sequencing with CNV PGxome
Clinical sensitivity cannot be precisely estimated as the adSTGD is not very common. Analytical sensitivity should be high because all mutations reported are detectable by this method. No gross deletions or duplications have been reported so far (Human Gene Mutation Database).
Testing Strategy
This test provides full coverage of all coding exons of the ELOVL4 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 patients with symptoms suggestive of Stargardt disease (STGD) are candidates.
All patients with symptoms suggestive of Stargardt disease (STGD) are candidates.
Gene
| Official Gene Symbol | OMIM ID |
|---|---|
| ELOVL4 | 605512 |
| Inheritance | Abbreviation |
|---|---|
| Autosomal Dominant | AD |
| Autosomal Recessive | AR |
| X-Linked | XL |
| Mitochondrial | MT |
Disease
| Name | Inheritance | OMIM ID |
|---|---|---|
| Stargardt Disease 3 | AD | 600110 |
Related Test
| Name |
|---|
| Flecked Retina Disorder Panel |
Citations
- Bernstein PS, Tammur J, Singh N, Hutchinson A, Dixon M, Pappas CM, Zabriskie NA, Zhang K, Petrukhin K, Leppert M, others. 2001. Diverse macular dystrophy phenotype caused by a novel complex mutation in the ELOVL4 gene. Investigative ophthalmology & visual science 42: 3331–3336. PubMed ID: 11726641
- Fishman GA, Farber M, Patel BS, Derlacki DJ. 1987. Visual acuity loss in patients with Stargardt’s macular dystrophy. Ophthalmology 94: 809–814. PubMed ID: 3658351
- Human Gene Mutation Database (Bio-base).
- Kaplan J, Gerber S, Larget-Piet D, Rozet JM, Dollfus H, Dufier JL, Odent S, Postel-Vinay A, Janin N, Briard ML. 1993. A gene for Stargardt’s disease (fundus flavimaculatus) maps to the short arm of chromosome 1. Nat. Genet. 5: 308–311. PubMed ID: 8275096
- Karan G, Lillo C, Yang Z, Cameron DJ, Locke KG, Zhao Y, Thirumalaichary S, Li C, Birch DG, Vollmer-Snarr HR, others. 2005. Lipofuscin accumulation, abnormal electrophysiology, and photoreceptor degeneration in mutant ELOVL4 transgenic mice: a model for macular degeneration. Proceedings of the National Academy of Sciences of the United States of America 102: 4164–4169. PubMed ID: 15749821
- Maugeri A. 2004. A Novel Mutation in the ELOVL4 Gene Causes Autosomal Dominant Stargardt-like Macular Dystrophy. Investigative Ophthalmology & Visual Science 45: 4263–4267. PubMed ID: 15557430
- Rossi S, Testa F, Attanasio M, Orrico A, Benedictis A de, Della Corte M, Simonelli F. 2012. Subretinal Fibrosis in Stargardt’s Disease with Fundus Flavimaculatus and ABCA4 Gene Mutation. Case reports in ophthalmology 3: 410–417. PubMed ID: 23341817
- Shastry BS. 2008. Evaluation of the common variants of the ABCA4 gene in families with Stargardt disease and autosomal recessive retinitis pigmentosa. International journal of molecular medicine 21: 715–720. PubMed ID: 18506364
- Stone EM, Nichols BE, Kimura AE, Weingeist TA, Drack A, Sheffield VC. 1994. Clinical features of a Stargardt-like dominant progressive macular dystrophy with genetic linkage to chromosome 6q. Arch. Ophthalmol. 112: 765–772. PubMed ID: 8002834
- Vasireddy V, Wong P, Ayyagari R. 2010. Genetics and molecular pathology of Stargardt-like macular degeneration. Progress in Retinal and Eye Research 29: 191–207. PubMed ID: 20096366
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
If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.
Specimen Types
Specimen Requirements and Shipping Details
PGxome (Exome) Sequencing Panel
PGnome (Genome) Sequencing Panel
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ORDER OPTIONS
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2) Select Additional Test Options
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