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Analysis of VSX1 Variations in Brazilian Subjects with Keratoconus
PURPOSE: To screen visual system homeobox 1 (VSX1) gene in Brazilian subjects affected with keratoconus (KCN). METHODS: Seventy-three patients with KCN and 106 healthy controls were enrolled in this study. Patients were diagnosed with KCN based on eye examination and corneal topographic features acc...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Medknow Publications & Media Pvt Ltd
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6058540/ https://www.ncbi.nlm.nih.gov/pubmed/30090183 http://dx.doi.org/10.4103/jovr.jovr_116_17 |
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author | da Silva, Dulceria Costa Gadelha, Bianca Nery Benevides Feitosa, Alex Felipe Barbosa da Silva, Rafaela Gomes Albuquerque, Tarsila Livia Paz e Santos, Débora Christina Pereira Fernandes Gadelha, Diego Nery Benevides Fonseca Schamber-Reis, Bruno Luiz |
author_facet | da Silva, Dulceria Costa Gadelha, Bianca Nery Benevides Feitosa, Alex Felipe Barbosa da Silva, Rafaela Gomes Albuquerque, Tarsila Livia Paz e Santos, Débora Christina Pereira Fernandes Gadelha, Diego Nery Benevides Fonseca Schamber-Reis, Bruno Luiz |
author_sort | da Silva, Dulceria Costa |
collection | PubMed |
description | PURPOSE: To screen visual system homeobox 1 (VSX1) gene in Brazilian subjects affected with keratoconus (KCN). METHODS: Seventy-three patients with KCN and 106 healthy controls were enrolled in this study. Patients were diagnosed with KCN based on eye examination and corneal topographic features according to Rabinowitz's criteria (K > 47.2, I-S > 1.4 and KISA > 100%). DNA from blood samples was extracted from donors, and the exons and exon-intron boundaries of VSX1 were sequenced. The potential impact of the identified amino acid changes was assessed with Poly-Phen2, SIFT, and PMUT analysis tools. Genotyping was confirmed by RLFP technique, which was also applied to genotype non-affected individuals. RESULTS: We found three non-synonymous substitutions (L68H, R131S, and D105E) in VSX1 exon 1, with L68H mutation as a novel variation in this gene. In silico analysis indicated that all variations found were predicted to be probably damaging to VSX1 structure and function. Examination of R131S and L68H variations segregating in one family suggested a strong effect of these variations in increasing disease severity in the proband, which presented bilateral KCN leading to corneal grafting before the age of sixteen. We found a novel synonymous substitution (P79P) and two previously described exonic polymorphisms, with unknown roles in VSX1 pathogenesis. CONCLUSION: VSX1 polymorphisms found in the Brazilian population support a genetic component in KCN pathogenesis. L68H is a novel mutation, and the phenotypic data suggest that this mutation might enhance disease severity when combined with other polymorphisms. However, further investigations are needed. |
format | Online Article Text |
id | pubmed-6058540 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Medknow Publications & Media Pvt Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-60585402018-08-08 Analysis of VSX1 Variations in Brazilian Subjects with Keratoconus da Silva, Dulceria Costa Gadelha, Bianca Nery Benevides Feitosa, Alex Felipe Barbosa da Silva, Rafaela Gomes Albuquerque, Tarsila Livia Paz e Santos, Débora Christina Pereira Fernandes Gadelha, Diego Nery Benevides Fonseca Schamber-Reis, Bruno Luiz J Ophthalmic Vis Res Original Article PURPOSE: To screen visual system homeobox 1 (VSX1) gene in Brazilian subjects affected with keratoconus (KCN). METHODS: Seventy-three patients with KCN and 106 healthy controls were enrolled in this study. Patients were diagnosed with KCN based on eye examination and corneal topographic features according to Rabinowitz's criteria (K > 47.2, I-S > 1.4 and KISA > 100%). DNA from blood samples was extracted from donors, and the exons and exon-intron boundaries of VSX1 were sequenced. The potential impact of the identified amino acid changes was assessed with Poly-Phen2, SIFT, and PMUT analysis tools. Genotyping was confirmed by RLFP technique, which was also applied to genotype non-affected individuals. RESULTS: We found three non-synonymous substitutions (L68H, R131S, and D105E) in VSX1 exon 1, with L68H mutation as a novel variation in this gene. In silico analysis indicated that all variations found were predicted to be probably damaging to VSX1 structure and function. Examination of R131S and L68H variations segregating in one family suggested a strong effect of these variations in increasing disease severity in the proband, which presented bilateral KCN leading to corneal grafting before the age of sixteen. We found a novel synonymous substitution (P79P) and two previously described exonic polymorphisms, with unknown roles in VSX1 pathogenesis. CONCLUSION: VSX1 polymorphisms found in the Brazilian population support a genetic component in KCN pathogenesis. L68H is a novel mutation, and the phenotypic data suggest that this mutation might enhance disease severity when combined with other polymorphisms. However, further investigations are needed. Medknow Publications & Media Pvt Ltd 2018 /pmc/articles/PMC6058540/ /pubmed/30090183 http://dx.doi.org/10.4103/jovr.jovr_116_17 Text en Copyright: © 2018 Journal of Ophthalmic and Vision Research http://creativecommons.org/licenses/by-nc-sa/4.0 This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms. |
spellingShingle | Original Article da Silva, Dulceria Costa Gadelha, Bianca Nery Benevides Feitosa, Alex Felipe Barbosa da Silva, Rafaela Gomes Albuquerque, Tarsila Livia Paz e Santos, Débora Christina Pereira Fernandes Gadelha, Diego Nery Benevides Fonseca Schamber-Reis, Bruno Luiz Analysis of VSX1 Variations in Brazilian Subjects with Keratoconus |
title | Analysis of VSX1 Variations in Brazilian Subjects with Keratoconus |
title_full | Analysis of VSX1 Variations in Brazilian Subjects with Keratoconus |
title_fullStr | Analysis of VSX1 Variations in Brazilian Subjects with Keratoconus |
title_full_unstemmed | Analysis of VSX1 Variations in Brazilian Subjects with Keratoconus |
title_short | Analysis of VSX1 Variations in Brazilian Subjects with Keratoconus |
title_sort | analysis of vsx1 variations in brazilian subjects with keratoconus |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6058540/ https://www.ncbi.nlm.nih.gov/pubmed/30090183 http://dx.doi.org/10.4103/jovr.jovr_116_17 |
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