Researchers discover gene responsible for rare, inherited eye disease

Ophthalmic images from 5 of the patients in the study demonstrate significant variability in the forms of retinal dystrophy. (Image credit: Bin Guan, PhD)

Researchers at the National Institutes of Health (NIH) and their colleagues have identified a gene responsible for some inherited retinal diseases (IRDs), which are a group of disorders that damage the retina and threaten vision.

While IRDs affect more than 2 million people around the world, each individual disease is rare, which complicates efforts to identify enough people to study and conduct clinical trials to develop treatment options for those conditions.

The study’s findings published in JAMA Ophthalmology.¹

In a small study of 6 participants who were not related, the researchers linked the gene UBAP1L to different forms of retinal dystrophies. The researchers noted in the study the patients presented with symptoms of retinal dystrophy that started in early adulthood, and progressed to severe vision loss by the time they reached late adulthood.

Overall, the goal of the research team was to provide a clinical and molecular characterization of 6 patients with IRDs with biallelic disease-causing variants in a novel candidate IRD disease gene.

“The patients in this study showed symptoms and features similar to other IRDs, but the cause of their condition was uncertain,” said Bin Guan, PhD, chief of the Ophthalmic Genomics Laboratory at NIH’s National Eye Institute (NEI) and a senior author of the report. “Now that we’ve identified the causative gene, we can study how the gene defect causes disease and, hopefully, develop treatment.”

The researchers noted that the identification of the involvement of the UBAP1L gene adds to the list of more than 280 genes responsible for this heterogeneous disease.¹

“These findings highlight the importance of providing genetic testing to our patients with retinal dystrophy, and the value of the clinic and lab working together to better understand retinal diseases,” said co-senior author on the paper, Laryssa A. Huryn, MD, an ophthalmologist at the NEI, part of the National Institutes of Health.

During a genetic evaluation of the 6 patients, the researchers reported that they found 4 variants in the UBAP1L gene, which encodes for a protein that is abundantly expressed in retina cells, including retinal pigment epithelium cells and photoreceptors.

The reseachers noted that study results reveal clinical and genetic evidence that loss of UBAP1L function was associated with inherited retinopathy in humans.¹

“These findings hold promise for improved clinical diagnostics, prognosis, and the potential development of targeted therapies for individuals affected by IRDs,” they wrote.

According to the researchers, additional research is needed to understand the UBAP1Lgene’s exact function, but scientists were able to determine that the identified variants likely cause the gene to produce protein that lacks function.

Future studies will also be informed by the fact that variants appear to be distinctive to geographic regions. Five of the 6 families in this study were from South or Southeastern Asia, or Polynesia, regions that have been underrepresented in genetic studies.¹

Investigators at Moorfields Eye Hospital and University College London collaborated on the research.

The study was funded by the Intramural Research Program at the NEI, and by NEI grants R01EY022356 and R01EY020540. Researchers at the University of Liverpool (UK), and Baylor College of Medicine in Houston, Texas, also contributed to the study.¹

Reference

Ullah E, Lin S, Lu J, Bender C, Webster AR, Malka S, Madusudhan S, Rees E, Williams D, Agather AR, Cukras CA, Hufnagel RB, Chen R, Huryn LA, Arno G, Guan B. “Biallelic loss-of-function variants in UBAP1L and nonsyndromic retinal dystrophies,” September 26, 2024, JAMA Ophthalmology. https://doi.org/10.1001/jamaophthalmol.2024.3836