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Contribution of a Novel B3GLCT Variant to Peters Plus Syndrome Discovered by a Combination of Next-Generation Sequencing and Automated Text Mining

Anterior segment dysgenesis (ASD) encompasses a spectrum of ocular disorders affecting the structures of the anterior eye chamber. Mutations in several genes, involved in eye development, are implicated in this disorder. ASD is often accompanied by diverse multisystemic symptoms and another genetic...

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Autores principales: Totoń-Żurańska, Justyna, Kapusta, Przemysław, Rybak-Krzyszkowska, Magda, Lorenc, Katarzyna, Machlowska, Julita, Skalniak, Anna, Filipek, Erita, Pawlik, Dorota, Wołkow, Paweł P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6928627/
https://www.ncbi.nlm.nih.gov/pubmed/31795264
http://dx.doi.org/10.3390/ijms20236006
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author Totoń-Żurańska, Justyna
Kapusta, Przemysław
Rybak-Krzyszkowska, Magda
Lorenc, Katarzyna
Machlowska, Julita
Skalniak, Anna
Filipek, Erita
Pawlik, Dorota
Wołkow, Paweł P.
author_facet Totoń-Żurańska, Justyna
Kapusta, Przemysław
Rybak-Krzyszkowska, Magda
Lorenc, Katarzyna
Machlowska, Julita
Skalniak, Anna
Filipek, Erita
Pawlik, Dorota
Wołkow, Paweł P.
author_sort Totoń-Żurańska, Justyna
collection PubMed
description Anterior segment dysgenesis (ASD) encompasses a spectrum of ocular disorders affecting the structures of the anterior eye chamber. Mutations in several genes, involved in eye development, are implicated in this disorder. ASD is often accompanied by diverse multisystemic symptoms and another genetic cause, such as variants in genes encoding collagen type IV. Thus, a wide spectrum of phenotypes and underlying genetic diversity make fast and proper diagnosis challenging. Here, we used AMELIE, an automatic text mining tool that enriches data with the most up-to-date information from literature, and wANNOVAR, which is based on well-documented databases and incorporates variant filtering strategy to identify genetic variants responsible for severely-manifested ASD in a newborn child. This strategy, applied to trio sequencing data in compliance with ACMG 2015 guidelines, helped us find two compound heterozygous variants of the B3GLCT gene, of which c.660+1G>A (rs80338851) was previously associated with the phenotype of Peters plus syndrome (PPS), while the second, NM_194318.3:c.755delC (p.T252fs), in exon 9 of the same gene was noted for the first time. PPS, a very rare subtype of ASD, is a glycosylation disorder, where the dysfunctional B3GLCT gene product, O-fucose-specific β-1,3-glucosyltransferase, is ineffective in providing a noncanonical quality control system for proper protein folding in cells. Our study expands the mutation spectrum of the B3GLCT gene related to PPS. We suggest that the implementation of automatic text mining tools in combination with careful variant filtering could help translate sequencing results into diagnosis, thus, considerably accelerating the diagnostic process and, thereby, improving patient management.
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spelling pubmed-69286272019-12-26 Contribution of a Novel B3GLCT Variant to Peters Plus Syndrome Discovered by a Combination of Next-Generation Sequencing and Automated Text Mining Totoń-Żurańska, Justyna Kapusta, Przemysław Rybak-Krzyszkowska, Magda Lorenc, Katarzyna Machlowska, Julita Skalniak, Anna Filipek, Erita Pawlik, Dorota Wołkow, Paweł P. Int J Mol Sci Communication Anterior segment dysgenesis (ASD) encompasses a spectrum of ocular disorders affecting the structures of the anterior eye chamber. Mutations in several genes, involved in eye development, are implicated in this disorder. ASD is often accompanied by diverse multisystemic symptoms and another genetic cause, such as variants in genes encoding collagen type IV. Thus, a wide spectrum of phenotypes and underlying genetic diversity make fast and proper diagnosis challenging. Here, we used AMELIE, an automatic text mining tool that enriches data with the most up-to-date information from literature, and wANNOVAR, which is based on well-documented databases and incorporates variant filtering strategy to identify genetic variants responsible for severely-manifested ASD in a newborn child. This strategy, applied to trio sequencing data in compliance with ACMG 2015 guidelines, helped us find two compound heterozygous variants of the B3GLCT gene, of which c.660+1G>A (rs80338851) was previously associated with the phenotype of Peters plus syndrome (PPS), while the second, NM_194318.3:c.755delC (p.T252fs), in exon 9 of the same gene was noted for the first time. PPS, a very rare subtype of ASD, is a glycosylation disorder, where the dysfunctional B3GLCT gene product, O-fucose-specific β-1,3-glucosyltransferase, is ineffective in providing a noncanonical quality control system for proper protein folding in cells. Our study expands the mutation spectrum of the B3GLCT gene related to PPS. We suggest that the implementation of automatic text mining tools in combination with careful variant filtering could help translate sequencing results into diagnosis, thus, considerably accelerating the diagnostic process and, thereby, improving patient management. MDPI 2019-11-28 /pmc/articles/PMC6928627/ /pubmed/31795264 http://dx.doi.org/10.3390/ijms20236006 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Communication
Totoń-Żurańska, Justyna
Kapusta, Przemysław
Rybak-Krzyszkowska, Magda
Lorenc, Katarzyna
Machlowska, Julita
Skalniak, Anna
Filipek, Erita
Pawlik, Dorota
Wołkow, Paweł P.
Contribution of a Novel B3GLCT Variant to Peters Plus Syndrome Discovered by a Combination of Next-Generation Sequencing and Automated Text Mining
title Contribution of a Novel B3GLCT Variant to Peters Plus Syndrome Discovered by a Combination of Next-Generation Sequencing and Automated Text Mining
title_full Contribution of a Novel B3GLCT Variant to Peters Plus Syndrome Discovered by a Combination of Next-Generation Sequencing and Automated Text Mining
title_fullStr Contribution of a Novel B3GLCT Variant to Peters Plus Syndrome Discovered by a Combination of Next-Generation Sequencing and Automated Text Mining
title_full_unstemmed Contribution of a Novel B3GLCT Variant to Peters Plus Syndrome Discovered by a Combination of Next-Generation Sequencing and Automated Text Mining
title_short Contribution of a Novel B3GLCT Variant to Peters Plus Syndrome Discovered by a Combination of Next-Generation Sequencing and Automated Text Mining
title_sort contribution of a novel b3glct variant to peters plus syndrome discovered by a combination of next-generation sequencing and automated text mining
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6928627/
https://www.ncbi.nlm.nih.gov/pubmed/31795264
http://dx.doi.org/10.3390/ijms20236006
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