eprintid: 1571745 rev_number: 24 eprint_status: archive userid: 608 dir: disk0/01/57/17/45 datestamp: 2017-08-30 15:17:18 lastmod: 2021-12-13 03:20:31 status_changed: 2017-08-30 15:17:18 type: article metadata_visibility: show creators_name: Holt, R creators_name: Ceroni, F creators_name: Bax, DA creators_name: Broadgate, S creators_name: Diaz, DG creators_name: Santos, C creators_name: Gerrelli, D creators_name: Ragge, NK title: New variant and expression studies provide further insight into the genotype-phenotype correlation in YAP1-related developmental eye disorders ispublished: pub divisions: UCL divisions: B02 divisions: D13 divisions: G22 keywords: Development, Gene expression, Medical genetics, Mutation note: Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. abstract: YAP1, which encodes the Yes-associated protein 1, is part of the Hippo pathway involved in development, growth, repair and homeostasis. Nonsense YAP1 mutations have been shown to co-segregate with autosomal dominantly inherited coloboma. Therefore, we screened YAP1 for variants in a cohort of 258 undiagnosed UK patients with developmental eye disorders, including anophthalmia, microphthalmia and coloboma. We identified a novel 1 bp deletion in YAP1 in a boy with bilateral microphthalmia and bilateral chorioretinal coloboma. This variant is located in the coding region of all nine YAP1 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 YAP1 in human eye development, we performed in situ hybridisation utilising human embryonic tissue, and observed expression in the developing eye, neural tube, brain and kidney. These findings help confirm the role of YAP1 and the Hippo developmental pathway in human eye development and its associated anomalies and demonstrate its expression during development in affected organ systems. date: 2017-08-11 date_type: published publisher: NATURE PUBLISHING GROUP official_url: http://dx.doi.org/10.1038/s41598-017-08397-w oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green article_type_text: Article verified: verified_manual elements_id: 1414814 doi: 10.1038/s41598-017-08397-w lyricists_name: Gerrelli, Dianne lyricists_name: Santos, Chloe lyricists_id: DGERR78 lyricists_id: CSANT19 actors_name: Bracey, Alan actors_id: ABBRA90 actors_role: owner full_text_status: public publication: Scientific Reports volume: 7 article_number: 7975 pages: 7 issn: 2045-2322 citation: Holt, R; Ceroni, F; Bax, DA; Broadgate, S; Diaz, DG; Santos, C; Gerrelli, D; Holt, R; Ceroni, F; Bax, DA; Broadgate, S; Diaz, DG; Santos, C; Gerrelli, D; Ragge, NK; - view fewer <#> (2017) New variant and expression studies provide further insight into the genotype-phenotype correlation in YAP1-related developmental eye disorders. Scientific Reports , 7 , Article 7975. 10.1038/s41598-017-08397-w <https://doi.org/10.1038/s41598-017-08397-w>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/1571745/1/s41598-017-08397-w.pdf