This article aims to provide insights about why different quality aspects matter, including the importance of covering difficult-to-sequence regions, as well as having explicit information regarding patient data privacy.
Differences in Quality
Does the test include relevant genes associated with IRD, including difficult-to-sequence regions?
A high-quality test should cover a wide range of genes (over 250) known to be associated with IRDs. Variants in the difficult-to-sequence RPGR gene explain >70% of cases of X-linked retinitis pigmentosa and >10% of all retinitis pigmentosa. Currently, there are several clinical trials recruiting patients with RPGR-related IRD for gene therapy. RPGR contains a difficult-to-sequence region called ORF15, which is a hotspot for disease-causing variants. Therefore, it is important to ensure the IRD panel you choose has deep, uniform coverage of this area.
Does the test include copy number variant detection and analysis of disease-causing non-coding variants?
Copy number variants (CNVs) play a significant role in the diagnosis of retinal dystrophies. In a recent series of 4,000 IRD patients, Blueprint Genetics found a diagnostic CNV in 4.8% of cases. Nearly half of these were <3 exons in size, making high-resolution analysis of critical importance. Additionally, coverage of non-coding (intronic) disease-causing variants, especially important for ABCA4, may not be included in all IRD panels. We have customized our My Retina Tracker Panel to include 128 non-coding variants across a number of genes.
Are details about the performance and limitations of the test readily available?
A publicly-available analytic validation should demonstrate the sequencing coverage and the sensitivity to detect single nucleotide variants, indels, and CNVs across all genes. This information should also be documented in the test result. Small differences in coverage may not seem significant, however, they translate to big differences at the sequence level and the diagnostic impact can be substantial. For example, the difference between 99% coverage and 97% coverage can mean some genes are not covered with sufficient sequencing depth to detect disease-causing variants.
Is genetic counseling available?
Genetic counseling is vital to helping patients understand their results, whether positive, negative or inconclusive. A genetic counselor will discuss the implications of genetic testing, provide clinical support to the patient and can identify at-risk family members. The ordering health care provider and patient will receive a comprehensive report summarizing the test results and associated medical recommendations. Expertise and specialized training in ophthalmic genetics is important when counseling patients with IRD.
Patient Privacy and Data Security
How will a patient’s data be used?
As sponsored testing programs have become more common, so have questions about privacy and security of the patient’s data. This information should be explicitly explained, including how patient data is secured, what patient data is used for and if identifiable patient data can be shared with third parties.
What patient information is provided to pharmaceutical company sponsors?
In Short: The My Retina Tracker® Program
- Provides individuals with a clinical diagnosis of inherited retinal disease (IRD) no-cost genetic testing and genetic counseling in collaboration with the Foundation Fighting Blindness and InformedDNA.
- Is currently sponsored by the Foundation Fighting Blindness, a nonprofit organization dedicated to finding treatments for IRD. Any new sponsors will be publically announced and a full list of sponsors will always be available on the program website.
- Patients have the opportunity to enroll in the Foundation Fighting Blindness My Retina Tracker Registry that aims to accelerate the delivery of therapies for IRDs.
- The Foundation Fighting Blindness has local chapters across the United States; joining a chapter is a great way to meet other people and families with inherited retinal diseases and find support and information on local resources.
- The My Retina Tracker Program uses Blueprint Genetics’ best-in-class Retinal Dystrophy Panel, which includes sequencing and CNV analysis of 322 genes.
- The My Retina Tracker panel includes excellent coverage of difficult-to-sequence regions including RPGR ORF15, analysis of the entire mitochondrial genome, high resolution CNV detection and disease-causing deep intronic variants – giving your patient the best chance at a molecular diagnosis.
Easy ordering online through our online portal Nucleus
Go to nucleus.blueprintgenetics.com to place your order.
To read more about eligibility, ordering, and to get a My Retina Tracker Program sample collection kit with pre-paid return shipment labels, visit the program website at blueprintgenetics.com/my-retina-tracker-program.