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The Genetic Landscape of Inherited Retinal Diseases in a Mexican Cohort: Genes, Mutations and Phenotypes

In this work, we aimed to provide the genetic diagnosis of a large cohort of patients affected with inherited retinal dystrophies (IRDs) from Mexico. Our data add valuable information to the genetic portrait in rare ocular diseases of Mesoamerican populations, which are mostly under-represented in g...

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Autores principales: Villanueva-Mendoza, Cristina, Tuson, Miquel, Apam-Garduño, David, de Castro-Miró, Marta, Tonda, Raul, Trotta, Jean Remi, Marfany, Gemma, Valero, Rebeca, Cortés-González, Vianney, Gonzàlez-Duarte, Roser
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8624043/
https://www.ncbi.nlm.nih.gov/pubmed/34828430
http://dx.doi.org/10.3390/genes12111824
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author Villanueva-Mendoza, Cristina
Tuson, Miquel
Apam-Garduño, David
de Castro-Miró, Marta
Tonda, Raul
Trotta, Jean Remi
Marfany, Gemma
Valero, Rebeca
Cortés-González, Vianney
Gonzàlez-Duarte, Roser
author_facet Villanueva-Mendoza, Cristina
Tuson, Miquel
Apam-Garduño, David
de Castro-Miró, Marta
Tonda, Raul
Trotta, Jean Remi
Marfany, Gemma
Valero, Rebeca
Cortés-González, Vianney
Gonzàlez-Duarte, Roser
author_sort Villanueva-Mendoza, Cristina
collection PubMed
description In this work, we aimed to provide the genetic diagnosis of a large cohort of patients affected with inherited retinal dystrophies (IRDs) from Mexico. Our data add valuable information to the genetic portrait in rare ocular diseases of Mesoamerican populations, which are mostly under-represented in genetic studies. A cohort of 144 unrelated probands with a clinical diagnosis of IRD were analyzed by next-generation sequencing using target gene panels (overall including 346 genes and 65 intronic sequences). Four unsolved cases were analyzed by whole-exome sequencing (WES). The pathogenicity of new variants was assessed by in silico prediction algorithms and classified following the American College of Medical Genetics and Genomics (ACMG) guidelines. Pathogenic or likely pathogenic variants were identified in 105 probands, with a final diagnostic yield of 72.9%; 17 cases (11.8%) were partially solved. Eighteen patients were clinically reclassified after a genetic diagnostic test (17.1%). In our Mexican cohort, mutations in 48 genes were found, with ABCA4, CRB1, RPGR and USH2A as the major contributors. Notably, over 50 new putatively pathogenic variants were identified. Our data highlight cases with relevant clinical and genetic features due to mutations in the RAB28 and CWC27 genes, enrich the novel mutation repertoire and expand the IRD landscape of the Mexican population.
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spelling pubmed-86240432021-11-27 The Genetic Landscape of Inherited Retinal Diseases in a Mexican Cohort: Genes, Mutations and Phenotypes Villanueva-Mendoza, Cristina Tuson, Miquel Apam-Garduño, David de Castro-Miró, Marta Tonda, Raul Trotta, Jean Remi Marfany, Gemma Valero, Rebeca Cortés-González, Vianney Gonzàlez-Duarte, Roser Genes (Basel) Article In this work, we aimed to provide the genetic diagnosis of a large cohort of patients affected with inherited retinal dystrophies (IRDs) from Mexico. Our data add valuable information to the genetic portrait in rare ocular diseases of Mesoamerican populations, which are mostly under-represented in genetic studies. A cohort of 144 unrelated probands with a clinical diagnosis of IRD were analyzed by next-generation sequencing using target gene panels (overall including 346 genes and 65 intronic sequences). Four unsolved cases were analyzed by whole-exome sequencing (WES). The pathogenicity of new variants was assessed by in silico prediction algorithms and classified following the American College of Medical Genetics and Genomics (ACMG) guidelines. Pathogenic or likely pathogenic variants were identified in 105 probands, with a final diagnostic yield of 72.9%; 17 cases (11.8%) were partially solved. Eighteen patients were clinically reclassified after a genetic diagnostic test (17.1%). In our Mexican cohort, mutations in 48 genes were found, with ABCA4, CRB1, RPGR and USH2A as the major contributors. Notably, over 50 new putatively pathogenic variants were identified. Our data highlight cases with relevant clinical and genetic features due to mutations in the RAB28 and CWC27 genes, enrich the novel mutation repertoire and expand the IRD landscape of the Mexican population. MDPI 2021-11-19 /pmc/articles/PMC8624043/ /pubmed/34828430 http://dx.doi.org/10.3390/genes12111824 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Villanueva-Mendoza, Cristina
Tuson, Miquel
Apam-Garduño, David
de Castro-Miró, Marta
Tonda, Raul
Trotta, Jean Remi
Marfany, Gemma
Valero, Rebeca
Cortés-González, Vianney
Gonzàlez-Duarte, Roser
The Genetic Landscape of Inherited Retinal Diseases in a Mexican Cohort: Genes, Mutations and Phenotypes
title The Genetic Landscape of Inherited Retinal Diseases in a Mexican Cohort: Genes, Mutations and Phenotypes
title_full The Genetic Landscape of Inherited Retinal Diseases in a Mexican Cohort: Genes, Mutations and Phenotypes
title_fullStr The Genetic Landscape of Inherited Retinal Diseases in a Mexican Cohort: Genes, Mutations and Phenotypes
title_full_unstemmed The Genetic Landscape of Inherited Retinal Diseases in a Mexican Cohort: Genes, Mutations and Phenotypes
title_short The Genetic Landscape of Inherited Retinal Diseases in a Mexican Cohort: Genes, Mutations and Phenotypes
title_sort genetic landscape of inherited retinal diseases in a mexican cohort: genes, mutations and phenotypes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8624043/
https://www.ncbi.nlm.nih.gov/pubmed/34828430
http://dx.doi.org/10.3390/genes12111824
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