University of Oklahoma Study Identifies 20 Novel Variants for Inherited Retinal Diseases

A new study out of the University of Oklahoma maps 20 new gene mutations contributing to rare inherited retinal diseases (IRDs). Researchers aim to use these findings to improve diagnostic accuracy and identify targets for future therapies. 

“These results clarify and confirm clinical diagnoses, aid in counseling patients on prognosis and family planning and guide treatment options,” team lead Lea D. Bennett, PhD said in a recent press release. “This study not only holds promise for affected individuals but also expands the mutation spectrum to guide understanding of IRDs.

Inherited retinal diseases are a group of vision-threating diseases that affect the light-sensitive layer in the back of the eye. These diseases are rare, affecting 1 out of 3,000 people. So far, 326 of the roughly 20,000 human genes have been linked to these disorders.

However, some patients with a clinical IRD diagnosis test negative for genetic mutations – the leading question behind Dr. Bennett’s research. 

Dr. Bennett and her team at the Dean McGee Eye Institute analyzed the genes of 103 unrelated patients with an IRD. Mutations were found in 70 patients, 20 of which were novel variations. These were associated with retinitis pigmentosa, cone-rod dystrophy, macular diseases and third-branch disorders. The most identified gene mutation was in ABCA4. New mutations were confirmed in four genes – ALMS1, GNAT1, RAX2 and RDH5.

Still, 33 samples from the study did not yield any genetic mutations. Dr. Bennett said there are several possible reasons to explain these inconsistencies, including misdiagnoses of late-onset IRDs or associations with gene mutations that have not yet been discovered – marking the importance of her findings to advance this field of research.

“There’s so much about hereditary retinal diseases that we don't know,” Dr. Bennett said. “The first step in developing new therapies for IRDs is to map the genetic mutations that trigger them.”

Currently, Luxturna is the only FDA-approved gene therapy for IRDs. The study team hopes this work can accelerate the search for more treatment options and help pharmaceutical companies identify clinical trial candidates.