{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T01:50:58Z","timestamp":1782179458870,"version":"3.54.5"},"reference-count":22,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,4,15]],"date-time":"2024-04-15T00:00:00Z","timestamp":1713139200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,4,15]],"date-time":"2024-04-15T00:00:00Z","timestamp":1713139200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Ophthalmol"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Purpose<\/jats:title>\n                <jats:p>The goal of the study was to search for novel bi-allelic <jats:italic>CRB1<\/jats:italic> mutations, and then to analyze the <jats:italic>CRB1<\/jats:italic> literature at the genotypic and phenotypic levels.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Approach<\/jats:title>\n                <jats:p>We screened various variables such as the <jats:italic>CRB1<\/jats:italic> mutation types, domains, exons, and genotypes and their relation with specific ocular phenotypes. An emphasis was given to the bi-allelic missense and nonsense mutations because of their high prevalence compared to other mutation types. Finally, we quantified the effect of various non-modifiable factors over the best-corrected visual acuity oculus uterque (BCVA OU) using multivariate linear regression models and identified genetic interactions.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>A novel bi-allelic missense in the exon 9 of <jats:italic>CRB1<\/jats:italic>; c.2936G\u2009&gt;\u2009A; p.(Gly979Asp) was found to be associated with rod-cone dystrophy (RCD). <jats:italic>CRB1<\/jats:italic> mutation type, exons, domains, and genotype distribution varied significantly according to fundus characteristics, such as peripheral pigmentation and condition, optic disc, vessels, macular condition, and pigmentation (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05). Of the 154 articles retrieved from PubMed, 96 studies with 439 bi-allelic <jats:italic>CRB1<\/jats:italic> patients were included. Missense mutations were significantly associated with an absence of macular pigments, pale optic disc, and periphery pigmentation, resulting in a higher risk of RCD (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05). In contrast, homozygous nonsense mutations were associated with macular pigments, periphery pigments, and a high risk of LCA (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05) and increased BCVA OU levels. We found that age, mutation types, and inherited retinal diseases were critical determinants of BCVA OU as they significantly increased it by 33% 26%, and 38%, respectively (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05). Loss of function alleles additively increased the risk of LCA, with nonsense having a more profound effect than indels. Finally, our analysis showed that p.(Cys948Tyr) and p.(Lys801Ter) and p.(Lys801Ter); p.(Cys896Ter) might interact to modify BCVA OU levels.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>This meta-analysis updated the literature and identified genotype-phenotype associations in bi-allelic <jats:italic>CRB1<\/jats:italic> patients.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12886-024-03419-4","type":"journal-article","created":{"date-parts":[[2024,4,15]],"date-time":"2024-04-15T08:01:58Z","timestamp":1713168118000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Genotype-phenotype associations in CRB1 bi-allelic patients: a novel mutation, a systematic review and meta-analysis"],"prefix":"10.1186","volume":"24","author":[{"given":"Ahmad","family":"Daher","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malak","family":"Banjak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinane","family":"Noureldine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Nehme","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Said","family":"El Shamieh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,4,15]]},"reference":[{"issue":"2","key":"3419_CR1","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1038\/13848","volume":"23","author":"AI den Hollander","year":"1999","unstructured":"den Hollander AI, et al. Mutations in a human homologue of Drosophila crumbs cause retinitis pigmentosa (RP12). Nat Genet. 1999;23(2):217\u201321.","journal-title":"Nat Genet"},{"issue":"2","key":"3419_CR2","doi-asserted-by":"publisher","first-page":"112","DOI":"10.12998\/wjcc.v3.i2.112","volume":"3","author":"OF Chacon-Camacho","year":"2015","unstructured":"Chacon-Camacho OF, Zenteno JC. Review and update on the molecular basis of Leber congenital amaurosis. World J Clin Cases. 2015;3(2):112\u201324.","journal-title":"World J Clin Cases"},{"issue":"2","key":"3419_CR3","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/j.ydbio.2019.05.008","volume":"453","author":"SH Cho","year":"2019","unstructured":"Cho SH, et al. Targeted deletion of Crb1\/Crb2 in the optic vesicle models key features of leber congenital amaurosis 8. 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The Institutional Review Board of Beirut Arab University approved our study (2017\u00a0H-0030-HS-R-0208). The participant provided written informed consent; their ophthalmic examinations were done at the Beirut Eye and ENT Specialist Hospital (Beirut, Lebanon).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Every participant gave his\/her written informed consent for publication of identifying information\/images in an online open-access publication.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"167"}}