{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T05:08:25Z","timestamp":1778216905309,"version":"3.51.4"},"reference-count":60,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T00:00:00Z","timestamp":1764288000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"IMO Grupo Miranza"},{"name":"Fundaci\u00f3 de Recerca de l\u2019Institut de Microcirurgia Ocular","award":["Fi-201401"],"award-info":[{"award-number":["Fi-201401"]}]},{"name":"Bernard Faure"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Pathogenic variants in Crumbs homolog 1 (CRB1) cause a wide range of severe ocular diseases, most commonly Leber congenital amaurosis and other forms of adult-onset macular dystrophy that lead to vision loss. Despite this broad clinical spectrum, the expression and function of CRB1 in retinal cells remains underexplored. In this study, we show a comprehensive characterization of CRB1 isoforms in several human retinal models like retinal organoids. Although CRB1 is predominantly expressed in photoreceptors and M\u00fcller glial cells, we also detected its expression in the human retinal pigment epithelium (RPE). Moreover, we observed defined expression patterns of CRB1 isoforms depending on the maturation stage of retinal cells, suggesting a role for this protein in development and differentiation. In this context, the less abundant and less studied isoform CRB1-C was the most highly expressed in early undifferentiated stages of photoreceptors and in RPE. Additionally, clinical and genetic evaluation of a cohort of 25 probands carrying pathogenic CRB1 variants allowed us to propose a genotype\u2013phenotype correlation between isoforms involvement and disease severity, and to the identification of four novel pathogenic variants: p.Met70ArgfsTer17, p.Cys136Phe, p.Cys248Ser and p.Gln1094Ter. Collectively, our data elucidate previously undescribed expression patterns of CRB1 isoforms during retinal cell differentiation and highlight key aspects of CRB1-associated inherited retinal dystrophies.<\/jats:p>","DOI":"10.3390\/ijms262311551","type":"journal-article","created":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T12:14:16Z","timestamp":1764332056000},"page":"11551","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Specific Pathogenicity Pattern of the Different CRB1 Isoforms Conditions Clinical Severity in Inherited Retinal Dystrophies"],"prefix":"10.3390","volume":"26","author":[{"given":"Laura","family":"Siles","sequence":"first","affiliation":[{"name":"Departament de Gen\u00e8tica, Institut de Microcirurgia Ocular, IMO Grupo Miranza, 08035 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sheila","family":"Ruiz-Nogales","sequence":"additional","affiliation":[{"name":"Departament de Gen\u00e8tica, Institut de Microcirurgia Ocular, IMO Grupo Miranza, 08035 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pilar","family":"M\u00e9ndez-Vendrell","sequence":"additional","affiliation":[{"name":"Departament de Gen\u00e8tica, Institut de Microcirurgia Ocular, IMO Grupo Miranza, 08035 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anniken","family":"Bur\u00e9s-Jelstrup","sequence":"additional","affiliation":[{"name":"Departament de Retina, Institut de Microcirurgia Ocular, IMO Grupo Miranza, 08035 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rafael","family":"Navarro","sequence":"additional","affiliation":[{"name":"Departament de Retina, Institut de Microcirurgia Ocular, IMO Grupo Miranza, 08035 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3818-3303","authenticated-orcid":false,"given":"Esther","family":"Pomares","sequence":"additional","affiliation":[{"name":"Departament de Gen\u00e8tica, Institut de Microcirurgia Ocular, IMO Grupo Miranza, 08035 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Ganapathi, M., Thomas-Wilson, A., Buchovecky, C., Dharmadhikari, A., Barua, S., Lee, W., Ruan, M.Z.C., Soucy, M., Ragi, S., and Tanaka, J. 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