When the Disease Does Not Follow the Textbook

Emerging therapies for inherited retinal degenerations are changing the way we talk to patients about these diseases. No longer are we regulated to confessing that there are no treatments and maybe something will come along in 5 years. Rather, we can now instill a sense of hope by highlighting the recent US Food and Drug Administration approval of the first gene augmentation therapy for retinal pigment epithelium –specific 65 kDa (RPE65)–associated retinopathy and the dozens of ongoing clinic trials for other genes. Our priorities have shifted to identifying causative genetic variants and determining which patients might be eligible for clinic trials. Genetic testing has improved to the point that we can now identify causative pathogenic variants in up to 75% of patients. However, this leaves about one-fourth of patients with unsolved cases and leaves us unable to determine if they could benefit from gene therapy. What accounts for these unsolved cases? Likely, some of these cases are not genetic b ut rather manifestations of old inflammatory processes. Others might consist of more complex genetic mechanisms not picked up by routine testing, such as large deletions, duplications, genes that act in a digenic manner, or deep intronic sequence variants.
Source: JAMA Ophthalmology - Category: Opthalmology Source Type: research