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:	Cristina Villanueva-Mendoza, Miquel Tuson, David Apam-Garduño, Marta de Castro-Miró, Raul Tonda, Jean Remi Trotta, Gemma Marfany, Rebeca Valero, Vianney Cortés-González, Roser Gonzàlez-Duarte
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	inherited retinal dystrophies genetic diagnosis whole-exome sequencing (WES) <i>RAB28</i> <i>CWC27</i> Genetics QH426-470
Acceso en línea:	https://doaj.org/article/be8d90764c1e4777a44d8388f0a034b8
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spelling	oai:doaj.org-article:be8d90764c1e4777a44d8388f0a034b82021-11-25T17:42:25ZThe Genetic Landscape of Inherited Retinal Diseases in a Mexican Cohort: Genes, Mutations and Phenotypes10.3390/genes121118242073-4425https://doaj.org/article/be8d90764c1e4777a44d8388f0a034b82021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4425/12/11/1824https://doaj.org/toc/2073-4425In 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 <i>ABCA4</i>, <i>CRB1, RPGR</i> and <i>USH2A</i> 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 <i>RAB28</i> and <i>CWC27</i> genes, enrich the novel mutation repertoire and expand the IRD landscape of the Mexican population.Cristina Villanueva-MendozaMiquel TusonDavid Apam-GarduñoMarta de Castro-MiróRaul TondaJean Remi TrottaGemma MarfanyRebeca ValeroVianney Cortés-GonzálezRoser Gonzàlez-DuarteMDPI AGarticleinherited retinal dystrophiesgenetic diagnosiswhole-exome sequencing (WES)<i>RAB28</i><i>CWC27</i>GeneticsQH426-470ENGenes, Vol 12, Iss 1824, p 1824 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	inherited retinal dystrophies genetic diagnosis whole-exome sequencing (WES) <i>RAB28</i> <i>CWC27</i> Genetics QH426-470
spellingShingle	inherited retinal dystrophies genetic diagnosis whole-exome sequencing (WES) <i>RAB28</i> <i>CWC27</i> Genetics QH426-470 Cristina Villanueva-Mendoza Miquel Tuson David Apam-Garduño Marta de Castro-Miró Raul Tonda Jean Remi Trotta Gemma Marfany Rebeca Valero Vianney Cortés-González Roser Gonzàlez-Duarte The Genetic Landscape of Inherited Retinal Diseases in a Mexican Cohort: Genes, Mutations and Phenotypes
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 <i>ABCA4</i>, <i>CRB1, RPGR</i> and <i>USH2A</i> 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 <i>RAB28</i> and <i>CWC27</i> genes, enrich the novel mutation repertoire and expand the IRD landscape of the Mexican population.
format	article
author	Cristina Villanueva-Mendoza Miquel Tuson David Apam-Garduño Marta de Castro-Miró Raul Tonda Jean Remi Trotta Gemma Marfany Rebeca Valero Vianney Cortés-González Roser Gonzàlez-Duarte
author_facet	Cristina Villanueva-Mendoza Miquel Tuson David Apam-Garduño Marta de Castro-Miró Raul Tonda Jean Remi Trotta Gemma Marfany Rebeca Valero Vianney Cortés-González Roser Gonzàlez-Duarte
author_sort	Cristina Villanueva-Mendoza
title	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_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_sort	genetic landscape of inherited retinal diseases in a mexican cohort: genes, mutations and phenotypes
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/be8d90764c1e4777a44d8388f0a034b8
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The Genetic Landscape of Inherited Retinal Diseases in a Mexican Cohort: Genes, Mutations and Phenotypes

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