{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T01:24:36Z","timestamp":1792027476538,"version":"4.4.0"},"reference-count":23,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,8,11]],"date-time":"2017-08-11T00:00:00Z","timestamp":1502409600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,8,11]],"date-time":"2017-08-11T00:00:00Z","timestamp":1502409600000},"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":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>YAP1<\/jats:italic>, which encodes the Yes-associated protein 1, is part of the Hippo pathway involved in development, growth, repair and homeostasis. Nonsense <jats:italic>YAP1<\/jats:italic> mutations have been shown to co-segregate with autosomal dominantly inherited coloboma. Therefore, we screened <jats:italic>YAP1<\/jats:italic> for variants in a cohort of 258 undiagnosed UK patients with developmental eye disorders, including anophthalmia, microphthalmia and coloboma. We identified a novel 1\u2009bp deletion in <jats:italic>YAP1<\/jats:italic> in a boy with bilateral microphthalmia and bilateral chorioretinal coloboma. This variant is located in the coding region of all nine <jats:italic>YAP1<\/jats:italic> spliceforms, and results in a frameshift and subsequent premature termination codon in each. The variant is predicted to result in the loss of part of the transactivation domain of YAP1, and sequencing of cDNA from the patient shows it does not result in nonsense mediated decay. To investigate the role of <jats:italic>YAP1<\/jats:italic> in human eye development, we performed <jats:italic>in situ<\/jats:italic> hybridisation utilising human embryonic tissue, and observed expression in the developing eye, neural tube, brain and kidney. These findings help confirm the role of <jats:italic>YAP1<\/jats:italic> and the Hippo developmental pathway in human eye development and its associated anomalies and demonstrate its expression during development in affected organ systems.<\/jats:p>","DOI":"10.1038\/s41598-017-08397-w","type":"journal-article","created":{"date-parts":[[2017,8,7]],"date-time":"2017-08-07T15:03:06Z","timestamp":1502118186000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["New variant and expression studies provide further insight into the genotype-phenotype correlation in YAP1-related developmental eye disorders"],"prefix":"10.1038","volume":"7","author":[{"given":"R.","family":"Holt","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Ceroni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. A.","family":"Bax","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Broadgate","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. Gold","family":"Diaz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Gerrelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N. K.","family":"Ragge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,8,11]]},"reference":[{"key":"8397_CR1","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1167\/iovs.10-5263","volume":"52","author":"SP Shah","year":"2011","unstructured":"Shah, S. P. et al. Anophthalmos, microphthalmos, and typical coloboma in the United Kingdom: a prospective study of incidence and risk. Invest Ophthalmol Vis Sci. \n                           52, 558\u201364 (2011).","journal-title":"Invest Ophthalmol Vis Sci."},{"key":"8397_CR2","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1038\/ng1120","volume":"33","author":"J Fantes","year":"2003","unstructured":"Fantes, J. et al. Mutations in SOX2 cause anophthalmia. Nat Genet. \n                           33, 461\u2013463 (2003).","journal-title":"Nat Genet."},{"key":"8397_CR3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/ajmg.a.30642","volume":"135","author":"NK Ragge","year":"2005","unstructured":"Ragge, N. K. et al. SOX2 anophthalmia syndrome. Am J Med Genet A. \n                           135, 1\u20137 (2005).","journal-title":"Am J Med Genet A."},{"key":"8397_CR4","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1016\/j.ajhg.2007.09.023","volume":"82","author":"P Bakrania","year":"2008","unstructured":"Bakrania, P. et al. Mutations in BMP4 cause eye, brain, and digit developmental anomalies: overlap between the BMP4 and hedgehog signaling pathways. Am J Hum Genet. \n                           82, 304\u2013319 (2008).","journal-title":"Am J Hum Genet."},{"key":"8397_CR5","doi-asserted-by":"publisher","first-page":"781","DOI":"10.1002\/humu.21280","volume":"31","author":"AW Wyatt","year":"2010","unstructured":"Wyatt, A. W., Osborne, R. J., Stewart, H. & Ragge, N. K. Bone morphogenetic protein 7 (BMP7) mutations are associated with variable ocular, brain, ear, palate, and skeletal anomalies. Hum Mutat. \n                           31, 781\u20137 (2010).","journal-title":"Hum Mutat."},{"key":"8397_CR6","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1111\/j.1399-0004.2012.01904.x","volume":"83","author":"N Chassaing","year":"2013","unstructured":"Chassaing, N. et al. Mutation analysis of the STRA6 gene in isolated and non-isolated anophthalmia\/microphthalmia. Clin Genet. \n                           83, 244\u201350 (2013).","journal-title":"Clin Genet."},{"key":"8397_CR7","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1016\/j.ajhg.2014.01.001","volume":"94","author":"KA Williamson","year":"2014","unstructured":"Williamson, K. A. et al. Heterozygous loss-of-function mutations in YAP1 cause both isolated and syndromic optic fissure closure defects. Am J Hum Genet. \n                           94, 295\u2013302 (2014).","journal-title":"Am J Hum Genet."},{"key":"8397_CR8","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1002\/(SICI)1096-8628(19971017)72:2<227::AID-AJMG19>3.0.CO;2-P","volume":"72","author":"D Ravine","year":"1997","unstructured":"Ravine, D., Ragge, N. K., Stephens, D., Oldridge, M. & Wilkie, A. O. Dominant coloboma-microphthalmos syndrome associated with sensorineural hearing loss, hematuria, and cleft lip\/palate. Am J Med Genet. \n                           72, 227\u201336 (1997).","journal-title":"Am J Med Genet."},{"key":"8397_CR9","first-page":"1","volume":"7","author":"JT Oatts","year":"2016","unstructured":"Oatts, J. T. et al. Novel heterozygous mutation in YAP1 in a family with isolated ocular colobomas. Ophthalmic Genet. \n                           7, 1\u20133 (2016).","journal-title":"Ophthalmic Genet."},{"key":"8397_CR10","doi-asserted-by":"publisher","first-page":"975","DOI":"10.1093\/hmg\/ddh106","volume":"13","author":"R Fossdal","year":"2004","unstructured":"Fossdal, R. et al. A novel TEAD1 mutation is the causative allele in Sveinsson\u2019s chorioretinal atrophy (helicoid peripapillary chorioretinal degeneration). Hum Mol Genet. \n                           13, 975\u201381 (2004).","journal-title":"Hum Mol Genet."},{"key":"8397_CR11","doi-asserted-by":"publisher","first-page":"6411","DOI":"10.1038\/ncomms7411","volume":"6","author":"U Basu-Roy","year":"2015","unstructured":"Basu-Roy, U. et al. Sox2 antagonizes the Hippo pathway to maintain stemness in cancer cells. Nat Commun. \n                           6, 6411 (2015).","journal-title":"Nat Commun."},{"key":"8397_CR12","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1002\/msb.201304750","volume":"9","author":"S Hauri","year":"2013","unstructured":"Hauri, S. et al. Interaction proteome of human Hippo signaling: modular control of the co-activator YAP1. Mol Syst Biol. \n                           9, 713 (2013).","journal-title":"Mol Syst Biol."},{"key":"8397_CR13","doi-asserted-by":"publisher","first-page":"2075","DOI":"10.1016\/j.celrep.2013.05.029","volume":"3","author":"E Seo","year":"2013","unstructured":"Seo, E. et al. SOX2 regulates YAP1 to maintain stemness and determine cell fate in the osteo-adipo lineage. Cell Rep. \n                           3, 2075\u201387 (2013).","journal-title":"Cell Rep."},{"key":"8397_CR14","doi-asserted-by":"publisher","first-page":"3021","DOI":"10.1242\/dev.119008","volume":"142","author":"JB Miesfeld","year":"2015","unstructured":"Miesfeld, J. B. et al. Yap and Taz regulate retinal pigment epithelial cell fate. Development. \n                           142, 3021\u20133032 (2015).","journal-title":"Development."},{"key":"8397_CR15","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1038\/nature14215","volume":"521","author":"S Porazinski","year":"2015","unstructured":"Porazinski, S. et al. YAP is essential for tissue tension to ensure vertebrate 3D body shape. Nature. \n                           521, 217\u201321 (2015).","journal-title":"Nature."},{"issue":"10","key":"8397_CR16","doi-asserted-by":"publisher","first-page":"e109811","DOI":"10.1371\/journal.pone.0109811","volume":"9","author":"VK Raghunathan","year":"2014","unstructured":"Raghunathan, V. K. et al. Involvement of YAP, TAZ and HSP90 in contact guidance and intercellular junction formation in corneal epithelial cells. 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Br J Ophthalmol. \n                           91, 1471\u20136 (2007).","journal-title":"Br J Ophthalmol."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-08397-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-08397-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-08397-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T08:28:51Z","timestamp":1671784131000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-08397-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,8,11]]},"references-count":23,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,12]]}},"alternative-id":["8397"],"URL":"https:\/\/doi.org\/10.1038\/s41598-017-08397-w","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,8,11]]},"assertion":[{"value":"22 March 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 July 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 August 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"7975"}}