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Whole-Exome Sequencing of Congenital Glaucoma Patients Reveals Hypermorphic Variants in GPATCH3, a New Gene Involved in Ocular and Craniofacial Development

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dc.contributor.author Ferré Fernández, Jesús José
dc.contributor.author Aroca Aguilar, José Daniel
dc.contributor.author Medina Trillo, Cristina
dc.contributor.author Bonet Fernández, Juan Manuel
dc.contributor.author Méndez Hernández, Carmen Dora
dc.contributor.author Morales Fernández, Laura
dc.contributor.author Cortón, Marta
dc.contributor.author Cabañero Valera, María José
dc.contributor.author Gut, Marta
dc.contributor.author Tonda, Raúl
dc.contributor.author Ayuso, Carmen
dc.contributor.author Coca Prados, Miguel
dc.contributor.author García Feijoo, Julián
dc.contributor.author Escribano Martínez, Julio
dc.date.accessioned 2017-07-21T07:14:31Z
dc.date.available 2017-07-21T07:14:31Z
dc.date.issued 2017-04-11
dc.identifier.citation Scientific Reports es_ES
dc.identifier.issn 2045-2322
dc.identifier.uri http://hdl.handle.net/10578/15031
dc.description.abstract Congenital glaucoma (CG) is a heterogeneous, inherited and severe optical neuropathy that originates from maldevelopment of the anterior segment of the eye. To identify new disease genes, we performed whole-exome sequencing of 26 unrelated CG patients. In one patient we identified two rare, recessive and hypermorphic coding variants in GPATCH3, a gene of unidentified function, and 5% of a second group of 170 unrelated CG patients carried rare variants in this gene. The recombinant GPATCH3 protein activated in vitro the proximal promoter of CXCR4, a gene involved in embryo neural crest cell migration. The GPATCH3 protein was detected in human tissues relevant to glaucoma (e.g., ciliary body). This gene was expressed in the dermis, skeletal muscles, periocular mesenchymal-like cells and corneal endothelium of early zebrafish embryos. Morpholino-mediated knockdown and transient overexpression of gpatch3 led to varying degrees of goniodysgenesis and ocular and craniofacial abnormalities, recapitulating some of the features of zebrafish embryos deficient in the glaucoma-related genes pitx2 and foxc1. In conclusion, our data suggest the existence of high genetic heterogeneity in CG and provide evidence for the role of GPATCH3 in this disease. We also show that GPATCH3 is a new gene involved in ocular and craniofacial development. es_ES
dc.format application/pdf es_ES
dc.language.iso en es_ES
dc.publisher Nature Publishing Group es_ES
dc.rights info:eu-repo/semantics/openAccess es_ES
dc.subject Medical genetics es_ES
dc.subject Genetics research es_ES
dc.subject Congenital glaucoma es_ES
dc.title Whole-Exome Sequencing of Congenital Glaucoma Patients Reveals Hypermorphic Variants in GPATCH3, a New Gene Involved in Ocular and Craniofacial Development es_ES
dc.type info:eu-repo/semantics/article es_ES
dc.identifier.ORCID http://orcid.org/0000-0002-8919-8134
dc.identifier.ORCID http://orcid.org/0000-0002-7772-5718
dc.identifier.DOI doi:10.1038/srep46175


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