Scaling new heights in the genetic diagnosis of inherited retinal dystrophies

During the last 20 years, our group has focused on identifying the genes and mutations causative of inherited retinal dystrophies (IRDs). By applying massive sequencing approaches (NGS) in more than 500 familial and sporadic cases, we attained high diagnostic efficiency (85%) with a custom target ge...

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Detalles Bibliográficos
Autores: Gonzàlez-Duarte, Roser, de Castro-Miró, Marta, Tuson, Miquel, Ramírez-Castañeda, Valeria, Valero-Gils, Rebeca, Marfany i Nadal, Gemma
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2019
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/196019
Acceso en línea:https://hdl.handle.net/2445/196019
Access Level:acceso abierto
Palabra clave:Malalties de la retina
Diagnòstic
Genètica
Retinal diseases
Diagnosis
Genetics
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spelling Scaling new heights in the genetic diagnosis of inherited retinal dystrophiesGonzàlez-Duarte, Roserde Castro-Miró, MartaTuson, MiquelRamírez-Castañeda, ValeriaValero-Gils, RebecaMarfany i Nadal, GemmaMalalties de la retinaDiagnòsticGenèticaRetinal diseasesDiagnosisGeneticsDuring the last 20 years, our group has focused on identifying the genes and mutations causative of inherited retinal dystrophies (IRDs). By applying massive sequencing approaches (NGS) in more than 500 familial and sporadic cases, we attained high diagnostic efficiency (85%) with a custom target gene panel and over 75% using whole exome sequencing (WES). Close to 40% of pathogenic alleles are novel mutations, which demand specific in silico tests and in vitro assays. Notably, missense variants are by far the most common type of mutation identified (around 40%), with small in-frame indels being less frequent (2%). To fill the gap of unsolved cases, when no candidate gene or only a single pathogenic allele has been identified, additional scientific and technical issues remain to be addressed. Reliable detection of genomic rearrangements and copy number variants (partial or complete), deep intronic mutations, variants that cause aberrant splicing events in retina-specific transcripts, functional assessment of hypomorphic missense alleles, mutations in regulatory sequences, the contribution of modifier genes to the IRD phenotype, and detection of low heteroplasmy mtDNA mutations are among the new challenges to be met.Springer Verlag2023202320192023info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersion5 p.application/pdfapplication/pdfhttps://hdl.handle.net/2445/196019Articles publicats en revistes (Genètica, Microbiologia i Estadística)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésVersió postprint del document publicat a: https://doi.org/10.1007/978-3-030-27378-1_35Advances in Experimental Medicine and Biology, 2019, vol. 1185, p. 215-219https://doi.org/10.1007/978-3-030-27378-1_35(c) Springer Verlag, 2019info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1960192026-05-29T05:05:01Z
dc.title.none.fl_str_mv Scaling new heights in the genetic diagnosis of inherited retinal dystrophies
title Scaling new heights in the genetic diagnosis of inherited retinal dystrophies
spellingShingle Scaling new heights in the genetic diagnosis of inherited retinal dystrophies
Gonzàlez-Duarte, Roser
Malalties de la retina
Diagnòstic
Genètica
Retinal diseases
Diagnosis
Genetics
title_short Scaling new heights in the genetic diagnosis of inherited retinal dystrophies
title_full Scaling new heights in the genetic diagnosis of inherited retinal dystrophies
title_fullStr Scaling new heights in the genetic diagnosis of inherited retinal dystrophies
title_full_unstemmed Scaling new heights in the genetic diagnosis of inherited retinal dystrophies
title_sort Scaling new heights in the genetic diagnosis of inherited retinal dystrophies
dc.creator.none.fl_str_mv Gonzàlez-Duarte, Roser
de Castro-Miró, Marta
Tuson, Miquel
Ramírez-Castañeda, Valeria
Valero-Gils, Rebeca
Marfany i Nadal, Gemma
author Gonzàlez-Duarte, Roser
author_facet Gonzàlez-Duarte, Roser
de Castro-Miró, Marta
Tuson, Miquel
Ramírez-Castañeda, Valeria
Valero-Gils, Rebeca
Marfany i Nadal, Gemma
author_role author
author2 de Castro-Miró, Marta
Tuson, Miquel
Ramírez-Castañeda, Valeria
Valero-Gils, Rebeca
Marfany i Nadal, Gemma
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Malalties de la retina
Diagnòstic
Genètica
Retinal diseases
Diagnosis
Genetics
topic Malalties de la retina
Diagnòstic
Genètica
Retinal diseases
Diagnosis
Genetics
description During the last 20 years, our group has focused on identifying the genes and mutations causative of inherited retinal dystrophies (IRDs). By applying massive sequencing approaches (NGS) in more than 500 familial and sporadic cases, we attained high diagnostic efficiency (85%) with a custom target gene panel and over 75% using whole exome sequencing (WES). Close to 40% of pathogenic alleles are novel mutations, which demand specific in silico tests and in vitro assays. Notably, missense variants are by far the most common type of mutation identified (around 40%), with small in-frame indels being less frequent (2%). To fill the gap of unsolved cases, when no candidate gene or only a single pathogenic allele has been identified, additional scientific and technical issues remain to be addressed. Reliable detection of genomic rearrangements and copy number variants (partial or complete), deep intronic mutations, variants that cause aberrant splicing events in retina-specific transcripts, functional assessment of hypomorphic missense alleles, mutations in regulatory sequences, the contribution of modifier genes to the IRD phenotype, and detection of low heteroplasmy mtDNA mutations are among the new challenges to be met.
publishDate 2019
dc.date.none.fl_str_mv 2019
2023
2023
2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/196019
url https://hdl.handle.net/2445/196019
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Versió postprint del document publicat a: https://doi.org/10.1007/978-3-030-27378-1_35
Advances in Experimental Medicine and Biology, 2019, vol. 1185, p. 215-219
https://doi.org/10.1007/978-3-030-27378-1_35
dc.rights.none.fl_str_mv (c) Springer Verlag, 2019
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) Springer Verlag, 2019
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 5 p.
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Springer Verlag
publisher.none.fl_str_mv Springer Verlag
dc.source.none.fl_str_mv Articles publicats en revistes (Genètica, Microbiologia i Estadística)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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