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标题：New variant and expression studies provide further insight into the genotype-phenotype correlation in YAP1-related developmental eye disorders
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作者：R. Holt ; F. Ceroni ; D. A. Bax 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2017
卷号：7
期号：1
DOI：10.1038/s41598-017-08397-w
语种：English
出版社：Springer Nature
摘要：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.