{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T20:48:19Z","timestamp":1792183699115,"version":"4.4.0"},"reference-count":28,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: Inherited retinal dystrophies (IRDs) include a clinically and genetically diverse array of conditions resulting in progressive visual impairment. The PROM1 gene is crucial for the development and maintenance of photoreceptors. Variants in PROM1 are linked to a wide phenotypic spectra of IRDs; however, the correlation between genotype and phenotype is not fully elucidated. Comprehending these relationships is essential for enhanced diagnostic precision, patient guidance, and formulation of focused treatments. Objective: This study aims to examine the genotype\u2013phenotype associations in patients with PROM1-associated IRDs. Clinical variability and inheritance patterns linked to different pathogenic variants are examined, aiming to clarify their different behaviors. Methods: We performed a retrospective investigation of patients identified as affected by PROM1-related IRDs. Thorough ophthalmologic assessments, including retinography, fundus autofluorescence, optical coherence tomography (OCT), and electrodiagnostic testing (EDT), were conducted. Genetic testing was performed via targeted gene panels or whole-exome sequencing. Variants were categorized based on ACMG criteria, and inheritance patterns were determined by familial segregation analysis. Clinical characteristics were analyzed among genotypic groups to ascertain potential phenotype\u2013genotype relationships. Results: All patients had pathogenic or likely pathogenic PROM1 mutations. Both autosomal dominant and autosomal recessive inheritance patterns were identified. Dominant pathogenic variants were predominantly linked to late-onset cone-rod dystrophy or macular dystrophy, whereas biallelic variants frequently resulted in early-onset severe rod\u2013cone dystrophy characterized by fast vision deterioration. A group of patients with the same genotypes displayed significant phenotypic variability, indicating the potential impact of modifier genes or environmental influences. Truncating mutations in the N-terminal region were significantly associated with earlier illness onset and greater functional impairment. Conclusions:\u00a0PROM1-related IRDs demonstrated significant clinical and genetic heterogeneity, with the route of inheritance and type of variant affecting disease severity and progression. Our findings underscore the significance of thorough genotypic and phenotypic characterization in afflicted individuals. A deeper comprehension of PROM1-related IRD disease pathways can enhance prognosis, direct clinical care, and facilitate the advancement of genotype-based therapy strategies.<\/jats:p>","DOI":"10.3390\/genes16111299","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T13:22:36Z","timestamp":1762176156000},"page":"1299","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Clinical and Molecular Findings in PROM1-Associated Inherited Retinal Dystrophies"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7938-876X","authenticated-orcid":false,"given":"Fabiana","family":"D\u2019Esposito","sequence":"first","affiliation":[{"name":"Imperial College Ophthalmic Research Group (ICORG) Unit, Imperial College, 153-173 Marylebone Rd, London NW15QH, UK"},{"name":"Department of Medicine and Surgery, University of Enna \u201cKore\u201d, Piazza dell\u2019Universit\u00e0, 94100 Enna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8424-0068","authenticated-orcid":false,"given":"Caterina","family":"Gagliano","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Enna \u201cKore\u201d, Piazza dell\u2019Universit\u00e0, 94100 Enna, Italy"},{"name":"Eye Center \u201cG.B. Morgagni-DSV\u201d, 95125 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Vallone","sequence":"additional","affiliation":[{"name":"Integrated Care Department of Laboratory and Transfusion Medicine, University Hospital Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6807-9455","authenticated-orcid":false,"given":"Francesco","family":"Cappellani","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Enna \u201cKore\u201d, Piazza dell\u2019Universit\u00e0, 94100 Enna, Italy"},{"name":"Eye Center \u201cG.B. Morgagni-DSV\u201d, 95125 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0059-5253","authenticated-orcid":false,"given":"Giuseppe","family":"Gagliano","sequence":"additional","affiliation":[{"name":"Eye Clinic, Catania University, Viale Carlo Azeglio Ciampi, 95121 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6463-2005","authenticated-orcid":false,"given":"Viviana","family":"Randazzo","sequence":"additional","affiliation":[{"name":"Ophthalmic Unit, A.O.R. Villa Sofia-Cervello, 90100 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Tognetto","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Health Sciences, University of Trieste, 34127 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4255-7312","authenticated-orcid":false,"given":"Gabriella","family":"Esposito","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, 80100 Naples, Italy"},{"name":"CEINGE-Advanced Biotechnologies Franco Salvatore, 80100 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0999-5545","authenticated-orcid":false,"given":"Marco","family":"Zeppieri","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Health Sciences, University of Trieste, 34127 Trieste, Italy"},{"name":"Department of Ophthalmology, University Hospital of Udine, 33100 Udine, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2305","DOI":"10.4103\/ijo.IJO_314_22","article-title":"Approach to inherited retinal diseases","volume":"70","author":"Ratra","year":"2022","journal-title":"Indian J. 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