{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T02:41:17Z","timestamp":1772160077727,"version":"3.50.1"},"reference-count":51,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,3,11]],"date-time":"2024-03-11T00:00:00Z","timestamp":1710115200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100020954","name":"START","doi-asserted-by":"publisher","award":["813490"],"award-info":[{"award-number":["813490"]}],"id":[{"id":"10.13039\/501100020954","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Leber congenital amaurosis (LCA) and early\u2010onset retinal degeneration (EORD) are inherited retinal diseases (IRD) characterized by early\u2010onset vision impairment. Herein, we studied 15 Saudi families by whole exome sequencing (WES) and run\u2010of\u2010homozygosity (ROH) detection via AutoMap in 12\/15 consanguineous families. This revealed (likely) pathogenic variants in 11\/15 families (73%). A potential founder variant was found in\n                    <jats:italic>RPGRIP1<\/jats:italic>\n                    . Homozygous pathogenic variants were identified in known IRD genes (\n                    <jats:italic>ATF6<\/jats:italic>\n                    ,\n                    <jats:italic>CRB1<\/jats:italic>\n                    ,\n                    <jats:italic>CABP4<\/jats:italic>\n                    ,\n                    <jats:italic>RDH12<\/jats:italic>\n                    ,\n                    <jats:italic>RIMS2<\/jats:italic>\n                    ,\n                    <jats:italic>RPGRIP1<\/jats:italic>\n                    ,\n                    <jats:italic>SPATA7)<\/jats:italic>\n                    . We established genotype\u2010driven clinical reclassifications for\n                    <jats:italic>ATF6<\/jats:italic>\n                    ,\n                    <jats:italic>CABP4<\/jats:italic>\n                    , and\n                    <jats:italic>RIMS2<\/jats:italic>\n                    . Specifically, we observed isolated IRD in the individual with the novel\n                    <jats:italic>RIMS2<\/jats:italic>\n                    variant, and we found a retina\u2010enriched\n                    <jats:italic>RIMS2<\/jats:italic>\n                    isoform conserved but not annotated in mouse. The latter illustrates potential different phenotypic consequences of pathogenic variants depending on the particular tissue\/cell\u2010type specific isoforms they affect. Lastly, a compound heterozygous genotype in\n                    <jats:italic>GUCY2D<\/jats:italic>\n                    in one non\u2010consanguineous family was demonstrated, and homozygous variants in novel candidate genes\n                    <jats:italic>ATG2B<\/jats:italic>\n                    and\n                    <jats:italic>RUFY3<\/jats:italic>\n                    were found in the two remaining consanguineous families. Reporting these genes will allow to validate them in other IRD cohorts. Finally, the missing heritability of the two unsolved IRD cases may be attributed to variants in non\u2010coding regions or structural variants that remained undetected, warranting future WGS studies.\n                  <\/jats:p>","DOI":"10.1111\/cge.14517","type":"journal-article","created":{"date-parts":[[2024,3,12]],"date-time":"2024-03-12T01:55:10Z","timestamp":1710208510000},"page":"127-139","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Autozygome\u2010guided exome\u2010first study in a consanguineous cohort with early\u2010onset retinal disease uncovers an isolated\n                    <i>RIMS2<\/i>\n                    phenotype and a retina\u2010enriched\n                    <i>RIMS2<\/i>\n                    isoform"],"prefix":"10.1111","volume":"106","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3934-0873","authenticated-orcid":false,"given":"Marta","family":"Del Pozo\u2010Valero","sequence":"first","affiliation":[{"name":"Department of Biomolecular Medicine Ghent University  Ghent Belgium"},{"name":"Center for Medical Genetics Ghent University Hospital  Ghent Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0266-4500","authenticated-orcid":false,"given":"Basamat","family":"Almoallem","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology College of Medicine, King Saud University (KSU)  Riyadh Saudi Arabia"},{"name":"Department of Ophthalmology King Saud University Medical City (KSUMC)  Riyadh Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4456-6159","authenticated-orcid":false,"given":"Alfredo","family":"Due\u00f1as Rey","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Medicine Ghent University  Ghent Belgium"},{"name":"Center for Medical Genetics Ghent University Hospital  Ghent Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0850-1745","authenticated-orcid":false,"given":"Quinten","family":"Mahieu","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Medicine Ghent University  Ghent Belgium"},{"name":"Center for Medical Genetics Ghent University Hospital  Ghent Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5758-0366","authenticated-orcid":false,"given":"Mattias","family":"Van Heetvelde","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Medicine Ghent University  Ghent Belgium"},{"name":"Center for Medical Genetics Ghent University Hospital  Ghent Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laila","family":"Jeddawi","sequence":"additional","affiliation":[{"name":"Pediatric Ophthalmology Division Dr. Sulaiman AL Habib Medical Group  AL Khobar Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0402-9006","authenticated-orcid":false,"given":"Miriam","family":"Bauwens","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Medicine Ghent University  Ghent Belgium"},{"name":"Center for Medical Genetics Ghent University Hospital  Ghent Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5609-6895","authenticated-orcid":false,"given":"Elfride","family":"De Baere","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Medicine Ghent University  Ghent Belgium"},{"name":"Center for Medical Genetics Ghent University Hospital  Ghent Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,3,11]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-030-27378-1_35"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2017.9"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.144105.112"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-018-0281-4"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-013-1344-x"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/0471142905.hg0612s75"},{"key":"e_1_2_9_8_1","article-title":"Identification of inherited retinal disease\u2010associated genetic variants in 11 candidate genes","volume":"9","author":"Astuti GDN","year":"2018","journal-title":"Genes 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