Inherited retinal diseases (IRDs) affect more than two million people worldwide, however because each individual disease is rare, it is difficult to identify enough people to study and to conduct clinical trials to develop treatment.
Now a small study of six unrelated participants, has linked the gene UBAP1L to different forms of inherited retinal dystrophies, with issues affecting the macula, the cone cells (cone dystrophy) or the rod cells (cone-rod dystrophy).
The study was conducted by scientists at the National Institutes of Health (NIH) and their colleagues at Moorfields Eye Hospital and University College London.1
Participating patients had symptoms of retinal dystrophy starting in early adulthood, progressing to severe vision loss by late adulthood.
Identifying the UBAP1L gene’s involvement adds to the list of more than 280 genes responsible for this heterogeneous disease.
“The patients in this study showed symptoms and features similar to other IRDs, but the cause of their condition was uncertain,” said Professor Bin Guan, 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.”
Identifying the UBAP1L gene’s involvement adds to the list of more than 280 genes responsible for this heterogeneous disease.
“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, Dr Laryssa A. Huryn, an ophthalmologist at the NEI.
Genetic evaluation of the six patients revealed four variants in the UBAP1L gene, which encodes for a protein that is abundantly expressed in retina cells, including retinal pigment epithelium cells and photoreceptors. More research is needed to understand the UBAP1L gene’s exact function, but the scientists were able to determine that the identified variants likely cause the gene to produce protein that lacks function.
Interestingly, the variants appear to be distinctive to geographic regions. Five of the six families in this study were from South or Southeastern Asia, or Polynesia, regions that have been underrepresented in genetic studies. This finding is likely to guide future studies
References
- Ullah E, Lin S, Guan B, et al. Biallelic loss-of-function variants in ubap1l and nonsyndromic retinal dystrophies. JAMA Ophthalmol. 2024 Sep 26:e243836. doi: 10.1001/jamaophthalmol.2024.3836.
