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Phenotype Analysis of Retinal Dystrophies in Light of the Underlying Genetic Defects: Application to Cone and Cone-Rod Dystrophies
Phenotypes observed in a large cohort of patients with cone and cone-rod dystrophies (COD/CORDs) are described based on multimodal retinal imaging features in order to help in analyzing massive next-generation sequencing data. Structural abnormalities of 58 subjects with molecular diagnosis of COD/C...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6801687/ https://www.ncbi.nlm.nih.gov/pubmed/31574917 http://dx.doi.org/10.3390/ijms20194854 |
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author | Boulanger-Scemama, Elise Mohand-Saïd, Saddek El Shamieh, Said Démontant, Vanessa Condroyer, Christel Antonio, Aline Michiels, Christelle Boyard, Fiona Saraiva, Jean-Paul Letexier, Mélanie Sahel, José-Alain Zeitz, Christina Audo, Isabelle |
author_facet | Boulanger-Scemama, Elise Mohand-Saïd, Saddek El Shamieh, Said Démontant, Vanessa Condroyer, Christel Antonio, Aline Michiels, Christelle Boyard, Fiona Saraiva, Jean-Paul Letexier, Mélanie Sahel, José-Alain Zeitz, Christina Audo, Isabelle |
author_sort | Boulanger-Scemama, Elise |
collection | PubMed |
description | Phenotypes observed in a large cohort of patients with cone and cone-rod dystrophies (COD/CORDs) are described based on multimodal retinal imaging features in order to help in analyzing massive next-generation sequencing data. Structural abnormalities of 58 subjects with molecular diagnosis of COD/CORDs were analyzed through specific retinal imaging including spectral-domain optical coherence tomography (SD-OCT) and fundus autofluorescence (BAF/IRAF). Findings were analyzed with the underlying genetic defects. A ring of increased autofluorescence was mainly observed in patients with CRX and GUCY2D mutations (33% and 22% of cases respectively). “Speckled” autofluorescence was observed with mutations in three different genes (ABCA4 64%; C2Orf71 and PRPH2, 18% each). Peripapillary sparing was only found in association with mutations in ABCA4, although only present in 40% of such genotypes. Regarding SD-OCT, specific outer retinal abnormalities were more commonly observed in particular genotypes: focal retrofoveal interruption and GUCY2D mutations (50%), foveal sparing and CRX mutations (50%), and outer retinal atrophy associated with hyperreflective dots and ABCA4 mutations (69%). This study outlines the phenotypic heterogeneity of COD/CORDs hampering statistical correlations. A larger study correlating retinal imaging with genetic results is necessary to identify specific clinical features that may help in selecting pathogenic variants generated by high-throughput sequencing. |
format | Online Article Text |
id | pubmed-6801687 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-68016872019-10-31 Phenotype Analysis of Retinal Dystrophies in Light of the Underlying Genetic Defects: Application to Cone and Cone-Rod Dystrophies Boulanger-Scemama, Elise Mohand-Saïd, Saddek El Shamieh, Said Démontant, Vanessa Condroyer, Christel Antonio, Aline Michiels, Christelle Boyard, Fiona Saraiva, Jean-Paul Letexier, Mélanie Sahel, José-Alain Zeitz, Christina Audo, Isabelle Int J Mol Sci Article Phenotypes observed in a large cohort of patients with cone and cone-rod dystrophies (COD/CORDs) are described based on multimodal retinal imaging features in order to help in analyzing massive next-generation sequencing data. Structural abnormalities of 58 subjects with molecular diagnosis of COD/CORDs were analyzed through specific retinal imaging including spectral-domain optical coherence tomography (SD-OCT) and fundus autofluorescence (BAF/IRAF). Findings were analyzed with the underlying genetic defects. A ring of increased autofluorescence was mainly observed in patients with CRX and GUCY2D mutations (33% and 22% of cases respectively). “Speckled” autofluorescence was observed with mutations in three different genes (ABCA4 64%; C2Orf71 and PRPH2, 18% each). Peripapillary sparing was only found in association with mutations in ABCA4, although only present in 40% of such genotypes. Regarding SD-OCT, specific outer retinal abnormalities were more commonly observed in particular genotypes: focal retrofoveal interruption and GUCY2D mutations (50%), foveal sparing and CRX mutations (50%), and outer retinal atrophy associated with hyperreflective dots and ABCA4 mutations (69%). This study outlines the phenotypic heterogeneity of COD/CORDs hampering statistical correlations. A larger study correlating retinal imaging with genetic results is necessary to identify specific clinical features that may help in selecting pathogenic variants generated by high-throughput sequencing. MDPI 2019-09-30 /pmc/articles/PMC6801687/ /pubmed/31574917 http://dx.doi.org/10.3390/ijms20194854 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 | Article Boulanger-Scemama, Elise Mohand-Saïd, Saddek El Shamieh, Said Démontant, Vanessa Condroyer, Christel Antonio, Aline Michiels, Christelle Boyard, Fiona Saraiva, Jean-Paul Letexier, Mélanie Sahel, José-Alain Zeitz, Christina Audo, Isabelle Phenotype Analysis of Retinal Dystrophies in Light of the Underlying Genetic Defects: Application to Cone and Cone-Rod Dystrophies |
title | Phenotype Analysis of Retinal Dystrophies in Light of the Underlying Genetic Defects: Application to Cone and Cone-Rod Dystrophies |
title_full | Phenotype Analysis of Retinal Dystrophies in Light of the Underlying Genetic Defects: Application to Cone and Cone-Rod Dystrophies |
title_fullStr | Phenotype Analysis of Retinal Dystrophies in Light of the Underlying Genetic Defects: Application to Cone and Cone-Rod Dystrophies |
title_full_unstemmed | Phenotype Analysis of Retinal Dystrophies in Light of the Underlying Genetic Defects: Application to Cone and Cone-Rod Dystrophies |
title_short | Phenotype Analysis of Retinal Dystrophies in Light of the Underlying Genetic Defects: Application to Cone and Cone-Rod Dystrophies |
title_sort | phenotype analysis of retinal dystrophies in light of the underlying genetic defects: application to cone and cone-rod dystrophies |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6801687/ https://www.ncbi.nlm.nih.gov/pubmed/31574917 http://dx.doi.org/10.3390/ijms20194854 |
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