Challenges confronting precision medicine in the context of inherited retinal disorders

ABSTRACT

“Tonight, I’m launching a new Precision Medicine Initiative to bring us closer to curing diseases like cancer and diabetes — and to give all of us access to the personalized information we need to keep ourselves and our families healthier.” - President Barack Obama, State of the Union Address, January 20, 2015. This new initiation of precision medicine has generated excitement and promises of improved health outcomes. The challenge is to use individual-specific information to provide optimal, cost-effective customized care. This entails a comprehensive knowledge of individual behaviors, diet and exposures as well as a complete past medical history of an individual and detailed (preferably quantitative) descriptions of clinical findings and measurements. The molecular genetics of an individual as well as that of diseased tissues such as cancers are an integral part of this program. Molecular diagnostics are especially important for individuals who are experiencing disorders that are clearly traceable to genetic variations. However, to realize the potential of combining genetics with non-genetic factors that contribute to disease, we will need to have a much better understanding of how genetic variants contribute to normal and pathologic physiology, and how to classify these genetic variants, which are often uncharacterized. In this paper we will consider the promise and challenges of molecular diagnostic testing for rare genetic disorders, with a focus on inherited retinal disorders (IRD), and leave the consideration of identifying, quantifying, and assessing non-genetic risk factors for disease to others.

KEYWORDS:

• Inherited retinal dystrophy
• retina
• genes
• molecular diagnosis
• genetic testing
• precision medicine
• retinitis pigmentosa
• next generation sequencing
• NGS

Financial & competing interests disclosure

J Chiang acknowledges the support from clients and support from Casey Eye Institute by grant P30 EY010572 from the National Institutes of Health (Bethesda, MD), and by unrestricted departmental funding from Research to Prevent Blindness (New York, NY). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.