Cone-Rod Dystrophy via the DRAM2 Gene
Summary and Pricing
Test Method
Exome Sequencing with CNV DetectionTest Code | Test Copy Genes | Test CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
---|---|---|---|---|---|
10443 | DRAM2 | 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
Cone-rod dystrophy (CORD/CRD) is a rare hereditary retinal disorder with a worldwide prevalence of ~1 in 40,000. CRD is characterized by dysfunction or degeneration of cone photoreceptors with relative preservation of rod function in the initial stages. The most common symptoms are photophobia and epiphora in bright light, decreased visual acuity, and dyschromatopsia. Fundus changes may vary from mild pigment granularity to a distinct atrophic lesion in the central macula. As the disease progresses, degeneration of rod photoreceptors also occurs and leads to progressive night blindness and peripheral visual field loss (Hamel. 2007. PubMed ID: 17270046).
Genetics
Non syndromic CRD is genetically heterogeneous and exhibits autosomal dominant (AD), autosomal recessive (AR) and, rarely, X-linked (XL) inheritance (Hamel. 2007. PubMed ID: 17270046). To date, over 25 genes have been implicated in different forms of CRD (RetNet). Due to the genetic heterogeneity, screening of all the CRD-associated genes is recommended. Most of the CRD-associated genes are also involved in other types of retinal dystrophies such as Retinitis Pigmentosa, macular dystrophies and cone dystrophies. Many of these genes encode proteins that have major roles in disc morphogenesis and the membrane- trafficking of photoreceptors (Sung and Chuang. 2010. PubMed ID: 20855501).
Bi-allelic pathogenic variants in DRAM2 cause adult-onset cone rod dystrophy with early macular involvement and associated central visual loss in the third or fourth decade of life (El-Asrag et al. 2015. PubMed ID: 25983245). Patients with DRAM2 cone rod dystrophy are typically asymptomatic in the first two decades of life (Sergouniotis et al. 2015. PubMed ID: 26720460). DRAM2 is a lysosomal protein expressed in both photoreceptor and retinal pigment epithelial cells (El-Asrag et al. 2015. PubMed ID: 25983245). DRAM2, unlike DRAM (damage-regulated autophagy modulator)-related proteins is not induced by p53 or p73. However, it remains possible that DRAM2 may still be a modulator of autophagy, perhaps in response to other stimuli (O'Prey et al. 2009. PubMed ID: 19556885; Crighton et al. 2006. PubMed ID: 16839881). DRAM2 might be involved in the process of photoreceptor renewal and recycling to preserve visual function (El-Asrag et al. 2015. PubMed ID: 25983245). To date, ~10 pathogenic variants (missense, nonsense and small in-frame and frameshift deletions) have been documented causative (Human Gene Mutation Database).
Clinical Sensitivity - Sequencing with CNV PGxome
Due to the genetic heterogeneity and limited number of reported cases, it is difficult to predict clinical sensitivity. Analytical sensitivity should be high as all reported pathogenic variants are detectable by sequencing.
To date, no copy number variants have been documented causative in this gene (Human Gene Mutation Database).
Testing Strategy
This test provides full coverage of all coding exons of the DRAM2 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 adult-onset Cone-rod dystrophy are candidates. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in DRAM2.
All patients with symptoms suggestive of adult-onset Cone-rod dystrophy are candidates. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in DRAM2.
Gene
Official Gene Symbol | OMIM ID |
---|---|
DRAM2 | 613360 |
Inheritance | Abbreviation |
---|---|
Autosomal Dominant | AD |
Autosomal Recessive | AR |
X-Linked | XL |
Mitochondrial | MT |
Disease
Name | Inheritance | OMIM ID |
---|---|---|
Cone-Rod Dystrophy 21 | AR | 616502 |
Related Tests
Citations
- Crighton et al. 2006. PubMed ID: 16839881
- El-Asrag et al. 2015. PubMed ID: 25983245
- Hamel. 2007. PubMed ID: 17270046
- Human Gene Mutation Database (Bio-base).
- O'Prey et al. 2009. PubMed ID: 19556885
- RetNet: Genes and Mapped Loci Causing Retinal Diseases.
- Sergouniotis et al. 2015. PubMed ID: 26720460
- Sung and Chuang. 2010. PubMed ID: 20855501
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
ORDER OPTIONS
View Ordering Instructions1) Select Test Type
2) Select Additional Test Options
No Additional Test Options are available for this test.