In a significant breakthrough, researchers at the National Institutes of Health (NIH) have discovered a gene associated with certain inherited retinal diseases (IRDs). These conditions, which damage the light-sensitive retina in the eye, affect over 2 million people worldwide. However, due to their rarity, conducting research and clinical trials for effective treatments has been challenging. This important finding was published in JAMA Ophthalmology.
What Are Inherited Retinal Diseases (IRDs)?
Inherited retinal diseases are a group of genetic disorders that impair vision by affecting the retina, the light-sensitive layer at the back of the eye. Here are some key points about IRDs:
- Impact on Vision: These diseases can lead to severe vision loss and even blindness.
- Genetic Basis: They are caused by mutations in specific genes that are essential for retinal health.
- Global Prevalence: While IRDs affect millions, each specific condition is relatively rare, complicating research efforts.
The Discovery of the UBAP1L Gene
In a study involving six unrelated participants, NIH researchers identified the UBAP1L gene as linked to various forms of retinal dystrophies. The patients exhibited symptoms like:
- Maculopathy: Issues affecting the macula, which is crucial for central vision used in activities such as reading.
- Cone Dystrophy: Problems affecting cone cells, responsible for color vision.
- Cone-Rod Dystrophy: A disorder impacting both cone and rod cells, the latter being essential for night vision.
Progression of Symptoms
The participants in the study began showing symptoms of retinal dystrophy in early adulthood, with the condition progressively worsening to severe vision loss by late adulthood. According to Dr. Bin Guan, chief of the Ophthalmic Genomics Laboratory at the NIH’s National Eye Institute (NEI):
“The patients in this study showed symptoms and features similar to other IRDs, but the cause of their condition was uncertain. Now that we’ve identified the causative gene, we can study how the gene defect causes disease and, hopefully, develop treatment.”
The Role of Genetic Testing in Understanding Retinal Diseases
The identification of the UBAP1L gene adds to a growing list of over 280 genes linked to inherited retinal diseases. Genetic testing is crucial for several reasons:
- Identifying Genetic Variants: In this study, the researchers found four variants in the UBAP1L gene among the participants. This gene encodes a protein that plays a vital role in retinal cells, including retinal pigment epithelium cells and photoreceptors.
- Collaborative Efforts: As emphasized by co-senior author Dr. Laryssa A. Huryn, providing genetic testing is essential for understanding retinal diseases and improving patient care.
Understanding the Variants
The researchers noted that the variants found in the UBAP1L gene likely lead to a non-functional protein. Although more studies are needed to clarify the exact role of this gene, the discovery paves the way for potential future therapies.
Geographic Diversity in Genetic Studies
The study also highlighted an important observation regarding the geographic backgrounds of the participants. Five of the six families were from South or Southeastern Asia or Polynesia, regions that have historically been underrepresented in genetic research. This suggests that:
- Genetic Variation: The variants in the UBAP1L gene may vary by geographic region, indicating the need for more inclusive studies.
- Future Research Directions: Further investigations could help understand how these genetic differences affect the presentation and treatment of IRDs.
Conclusion
The discovery of the UBAP1L gene marks an important advancement in the quest to understand and treat inherited retinal diseases. By shedding light on the genetic basis of these conditions, researchers are one step closer to developing targeted genetic testing, clinical trials, and new therapies. This research not only benefits those affected by IRDs but also emphasizes the importance of diverse representation in genetic studies.
References
- Ullah, E., Lin, S., Lu, J., Bender, C., Webster, A. R., Malka, S., Madhusudhan, S., Rees, E., Williams, D., Agather, A. R., Cukras, C. A., Hufnagel, R. B., Chen, R., Huryn, L. A., Arno, G., & Guan, B. (2024). Biallelic Loss-of-Function Variants in UBAP1L and Nonsyndromic Retinal Dystrophies. JAMA Ophthalmology. DOI: 10.1001/jamaophthalmol.2024.3836.
The study was co-led by investigators at Moorfields Eye Hospital and University College London, with funding from the Intramural Research Program at the NEI and additional NEI grants.