{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:21:49Z","timestamp":1790814109546,"version":"4.1.0"},"reference-count":35,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,8,17]],"date-time":"2020-08-17T00:00:00Z","timestamp":1597622400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["R21HD099701"],"award-info":[{"award-number":["R21HD099701"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["R01EY025718"],"award-info":[{"award-number":["R01EY025718"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Ocular coloboma is caused by failure of optic fissure closure during development and recognized as part of the microphthalmia, anophthalmia, and coloboma (MAC) spectrum. While many genes are known to cause colobomatous microphthalmia, relatively few have been reported in coloboma with normal eye size. Genetic analysis including trio exome sequencing and Sanger sequencing was undertaken in a family with two siblings affected with bilateral coloboma of the iris, retina, and choroid. Pathogenic variants in MAC genes were excluded. Trio analysis identified compound heterozygous donor splice site variants in\n                    <jats:italic>CDON,<\/jats:italic>\n                    a cell\u2010surface receptor known to function in the Sonic Hedgehog pathway, c.928\u2009+\u20091G\u2009&gt;\u2009A and c.2650\u2009+\u20091G\u2009&gt;\u2009T, in both affected individuals. Heterozygous missense and truncating\n                    <jats:italic>CDON<\/jats:italic>\n                    variants are associated with dominant holoprosencephaly (HPE) with incomplete penetrance and\n                    <jats:italic>Cdon\u2212\/\u2212<\/jats:italic>\n                    mice display variable HPE and coloboma. A homozygous nonsense allele of uncertain significance was recently identified in a consanguineous patient with coloboma and a second molecular diagnosis. We report the first compound heterozygous variants in\n                    <jats:italic>CDON<\/jats:italic>\n                    as a cause of isolated coloboma.\n                    <jats:italic>CDON<\/jats:italic>\n                    is the first HPE gene identified to cause recessive coloboma. Given the phenotypic overlap, further examination of HPE genes in coloboma is indicated.\n                  <\/jats:p>","DOI":"10.1111\/cge.13824","type":"journal-article","created":{"date-parts":[[2020,7,30]],"date-time":"2020-07-30T01:27:59Z","timestamp":1596072479000},"page":"486-492","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Compound heterozygous splicing\n                    <scp>\n                      <i>CDON<\/i>\n                    <\/scp>\n                    variants result in isolated ocular coloboma"],"prefix":"10.1111","volume":"98","author":[{"given":"Linda M.","family":"Reis","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Children's Research Institute Medical College of Wisconsin and Children's Wisconsin  Milwaukee Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald","family":"Basel","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Children's Research Institute Medical College of Wisconsin and Children's Wisconsin  Milwaukee Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"McCarrier","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Children's Research Institute Medical College of Wisconsin and Children's Wisconsin  Milwaukee Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David V.","family":"Weinberg","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences Medical College of Wisconsin  Milwaukee Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0531-3586","authenticated-orcid":false,"given":"Elena V.","family":"Semina","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Children's Research Institute Medical College of Wisconsin and Children's Wisconsin  Milwaukee Wisconsin USA"},{"name":"Department of Ophthalmology and Visual Sciences Medical College of Wisconsin  Milwaukee Wisconsin USA"},{"name":"Department of Cell Biology, Neurobiology and Anatomy Medical College of Wisconsin  Milwaukee Wisconsin 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