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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
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.
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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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