New variant and expression studies provide further insight into the genotype-phenotype correlation in YAP1-related developmental eye disorders

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...

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Autores principales:	R. Holt, F. Ceroni, D. A. Bax, S. Broadgate, D. Gold Diaz, C. Santos, D. Gerrelli, N. K. Ragge
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a311b793cca04d9788f831add14f8a0f
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spelling	oai:doaj.org-article:a311b793cca04d9788f831add14f8a0f2021-12-02T15:18:54ZNew variant and expression studies provide further insight into the genotype-phenotype correlation in YAP1-related developmental eye disorders10.1038/s41598-017-08397-w2045-2322https://doaj.org/article/a311b793cca04d9788f831add14f8a0f2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08397-whttps://doaj.org/toc/2045-2322Abstract 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.R. HoltF. CeroniD. A. BaxS. BroadgateD. Gold DiazC. SantosD. GerrelliN. K. RaggeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-7 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q R. Holt F. Ceroni D. A. Bax S. Broadgate D. Gold Diaz C. Santos D. Gerrelli N. K. Ragge New variant and expression studies provide further insight into the genotype-phenotype correlation in YAP1-related developmental eye disorders
description	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.
format	article
author	R. Holt F. Ceroni D. A. Bax S. Broadgate D. Gold Diaz C. Santos D. Gerrelli N. K. Ragge
author_facet	R. Holt F. Ceroni D. A. Bax S. Broadgate D. Gold Diaz C. Santos D. Gerrelli N. K. Ragge
author_sort	R. Holt
title	New variant and expression studies provide further insight into the genotype-phenotype correlation in YAP1-related developmental eye disorders
title_short	New variant and expression studies provide further insight into the genotype-phenotype correlation in YAP1-related developmental eye disorders
title_full	New variant and expression studies provide further insight into the genotype-phenotype correlation in YAP1-related developmental eye disorders
title_fullStr	New variant and expression studies provide further insight into the genotype-phenotype correlation in YAP1-related developmental eye disorders
title_full_unstemmed	New variant and expression studies provide further insight into the genotype-phenotype correlation in YAP1-related developmental eye disorders
title_sort	new variant and expression studies provide further insight into the genotype-phenotype correlation in yap1-related developmental eye disorders
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/a311b793cca04d9788f831add14f8a0f
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New variant and expression studies provide further insight into the genotype-phenotype correlation in YAP1-related developmental eye disorders

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