{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T02:49:57Z","timestamp":1771296597818,"version":"3.50.1"},"reference-count":36,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2020,6,1]],"date-time":"2020-06-01T00:00:00Z","timestamp":1590969600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Fundaci\u00f3n Mar\u00eda Cristina Masaveu Peterson"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Ophthalmologica"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Purpose<\/jats:title><jats:p>In the era of precision medicine, genomic characterization of blind patients is critical. Here, we evaluate the effects of comprehensive genetic analysis on the etiologic diagnosis of potentially hereditary vision loss and its impact on clinical management.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We studied 100 non\u2010syndromic and syndromic Spanish patients with a clinical diagnosis of blindness caused by alterations on the retina, choroid, vitreous and\/or optic nerve. We used a next\u2010generation sequencing (NGS) panel (OFTALMOgenics\u2122), developed and validated within this study, including up to 362 genes previously associated with these conditions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified the genetic cause of blindness in 45% of patients (45\/100). A total of 28.9% of genetically diagnosed cases (13\/45) were syndromic and, of those, in 30.8% (4\/13) extraophthalmic features had been overlooked and\/or not related to visual impairment before genetic testing, including cases with Mainzer\u2010Saldino, Bardet\u2010Biedl, mucolipidosis and MLCRD syndromes. In two additional cases\u2013syndromic blindness had been proposed before, but not specifically diagnosed, and one patient with Heimler syndrome had been misdiagnosed as an Usher case before testing. 33.3% of the genetically diagnosed patients (15\/45) had causative variants in genes targeted by clinical trials exploring the curative potential of gene therapy approaches.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Comprehensive genomic testing provided clinically relevant insights in a large proportion of blind patients, identifying potential therapeutic opportunities or previously undiagnosed syndromes in 42.2% of the genetically diagnosed cases (19\/45).<\/jats:p><\/jats:sec>","DOI":"10.1111\/aos.14479","type":"journal-article","created":{"date-parts":[[2020,6,2]],"date-time":"2020-06-02T06:13:23Z","timestamp":1591078403000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Comprehensive genomic diagnosis of inherited retinal and optical nerve disorders reveals hidden syndromes and personalized therapeutic options"],"prefix":"10.1111","volume":"98","author":[{"given":"Marta","family":"Di\u00f1eiro","sequence":"first","affiliation":[{"name":"Instituto de Medicina Oncol\u00f3gica y Molecular de Asturias (IMOMA) S. A. Oviedo Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raquel","family":"Cap\u00edn","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Oncol\u00f3gica y Molecular de Asturias (IMOMA) S. A. Oviedo Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guadalupe \u00c1.","family":"Cifuentes","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Oncol\u00f3gica y Molecular de Asturias (IMOMA) S. A. Oviedo Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beatriz","family":"Fern\u00e1ndez\u2010Vega","sequence":"additional","affiliation":[{"name":"Instituto Oftalmol\u00f3gico Fern\u00e1ndez\u2010Vega (IOFV) Oviedo Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva","family":"Villota","sequence":"additional","affiliation":[{"name":"Instituto Oftalmol\u00f3gico Fern\u00e1ndez\u2010Vega (IOFV) Oviedo Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Otero","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Oncol\u00f3gica y Molecular de Asturias (IMOMA) S. A. Oviedo Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adri\u00e1n","family":"Santiago","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Oncol\u00f3gica y Molecular de Asturias (IMOMA) S. A. Oviedo Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia C.","family":"Pruneda","sequence":"additional","affiliation":[{"name":"Disease Research And Medicine (DREAMgenics) S. L. Oviedo Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Castillo","sequence":"additional","affiliation":[{"name":"Disease Research And Medicine (DREAMgenics) S. L. Oviedo Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M\u00f3nica","family":"Viejo\u2010D\u00edaz","sequence":"additional","affiliation":[{"name":"Hospital Universitario Central de Asturias Oviedo Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"In\u00e9s","family":"Hernando","sequence":"additional","affiliation":[{"name":"Hospital Universitario Central de Asturias Oviedo Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noelia S.","family":"Dur\u00e1n","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Oncol\u00f3gica y Molecular de Asturias (IMOMA) S. A. Oviedo Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebeca","family":"\u00c1lvarez","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Oncol\u00f3gica y Molecular de Asturias (IMOMA) S. A. Oviedo Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia G.","family":"Lago","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Oncol\u00f3gica y Molecular de Asturias (IMOMA) S. A. Oviedo Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gonzalo R.","family":"Ord\u00f3\u00f1ez","sequence":"additional","affiliation":[{"name":"Disease Research And Medicine (DREAMgenics) S. L. Oviedo Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u00c1lvaro","family":"Fern\u00e1ndez\u2010Vega","sequence":"additional","affiliation":[{"name":"Instituto Oftalmol\u00f3gico Fern\u00e1ndez\u2010Vega (IOFV) Oviedo Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rub\u00e9n","family":"Cabanillas","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Oncol\u00f3gica y Molecular de Asturias (IMOMA) S. A. Oviedo Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7561-7759","authenticated-orcid":false,"given":"Juan","family":"Cadi\u00f1anos","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Oncol\u00f3gica y Molecular de Asturias (IMOMA) S. A. Oviedo Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,6]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-7-8"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3031"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1312543"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.14462"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2011.86"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.291"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12920-018-0375-5"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1586\/14737159.2015.1081057"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2014.172"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40942-017-0087-6"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1001\/archophthalmol.2012.2434"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23349"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/ceo.12159"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/IAE.0000000000001341"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.22608\/APO.201851"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2018.51"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.15"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0327-9"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-34380-0"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2014.02.008"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13426"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.03.006"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2015.08.011"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaophthalmol.2014.2814"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)31868-8"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1097\/ICU.0000000000000404"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22294"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmoldx.2012.04.006"},{"key":"e_1_2_5_31_1","first-page":"783","article-title":"Nonsyndromic retinitis pigmentosa is highly prevalent in the Jerusalem region with a high frequency of founder mutations","volume":"21","author":"Sharon D","year":"2015","journal-title":"Mol Vis"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2012.05.047"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0051422"},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2018.03.005"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/78182"},{"key":"e_1_2_5_36_1","doi-asserted-by":"publisher","DOI":"10.3109\/08820538.2014.959202"},{"key":"e_1_2_5_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-015-1586-x"}],"container-title":["Acta Ophthalmologica"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Faos.14479","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/aos.14479","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/aos.14479","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/aos.14479","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T21:58:54Z","timestamp":1693864734000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/aos.14479"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6]]},"references-count":36,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["10.1111\/aos.14479"],"URL":"https:\/\/doi.org\/10.1111\/aos.14479","archive":["Portico"],"relation":{},"ISSN":["1755-375X","1755-3768"],"issn-type":[{"value":"1755-375X","type":"print"},{"value":"1755-3768","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6]]},"assertion":[{"value":"2019-12-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-04-29","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-06-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}