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NEI-supported findings pave the way for genetic testing, clinical trials, and therapy development
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September 26, 2024
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<a href="/about/news-and-events/news?initiatives=224" hreflang="en">Ophthalmic Genetics Laboratory</a>
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<img src="https://www.nei.nih.gov/sites/default/files/styles/large/public/2024-09/variability%20IRD.jpg?itok=b5l9gwUM" alt="Ophthalmic images from the study probands exhibit variable forms of retinal dystrophy as shown on fundus photos, fundus autoflorescence and optical coherence tomography." width="1044" height="878">
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<p>Ophthalmic images from the study probands exhibit variable forms of retinal dystrophy. Bin Guan, Ph.D.</p>
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<p>Scientists at the National Eye Institute and their colleagues have identified a gene responsible for some inherited retinal diseases (IRDs), which are a group of disorders that damage the eye’s light-sensing retina and threatens vision. Though IRDs affect more than 2 million people worldwide, each individual disease is rare, complicating efforts to identify enough people to study and conduct clinical trials to develop treatment. The study’s findings published today in <em>JAMA Ophthalmology</em>.</p><p>In a small study of six unrelated participants, researchers linked the gene <em>UBAP1L</em> to different forms of retinal dystrophies, with issues affecting the macula, the part of the eye used for central vision such as for reading (maculopathy), issues affecting the cone cells that enable color vision (cone dystrophy) or a disorder that also affects the rod cells that enable night vision (cone-rod dystrophy). The patients had symptoms of retinal dystrophy starting in early adulthood, progressing to severe vision loss by late adulthood.</p><p>“The patients in this study showed symptoms and features similar to other IRDs, but the cause of their condition was uncertain,” said Bin Guan, Ph.D., 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.”</p><p>Identifying the <em>UBAP1L </em>gene’s involvement adds to the list of more than 280 genes responsible for this heterogeneous disease.</p><p>“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, M.D., an ophthalmologist at the NEI, part of the National Institutes of Health.</p><p>Genetic evaluation of the six patients revealed four variants in the <em>UBAP1L</em> 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 <em>UBAP1L</em> gene’s exact function, but scientists were able to determine that the identified variants likely cause the gene to produce protein that lacks function.</p><p>Future studies will also be informed by the fact that 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.</p><p>The research was co-led by investigators at Moorfields Eye Hospital and University College London.</p><p>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, Houston, Tx also contributed to this report.</p><p> </p><p>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. <a href="https://jamanetwork.com/journals/jamaophthalmology/article-abstract/2824094">https://jamanetwork.com/journals/jamaophthalmology/article-abstract/2824094</a></p><p>NEI leads the federal government’s research on the visual system and eye diseases. NEI supports basic and clinical science programs to develop sight-saving treatments and address special needs of people with vision loss. For more information, visit <a href="/">https://www.nei.nih.gov</a>.</p><p>About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit <a href="https://www.nih.gov/">https://www.nih.gov/</a>.</p><p>NIH…Turning Discovery Into Health®</p>
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