Development and application of a next-generation-sequencing (NGS) approach to detect known and novel gene defects underlying retinal diseases

This is an Open Access article distributed under the terms of the Creative Commons Attribution License.-- et. al.

Detalles Bibliográficos
Autores: Audo, Isabelle, Bhattacharya, Shom Shanker, Zeitz, Christina
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2012
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/121645
Acceso en línea:http://hdl.handle.net/10261/121645
Access Level:acceso abierto
Palabra clave:NGS
Retinal disorders
Diagnostic tool
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spelling Development and application of a next-generation-sequencing (NGS) approach to detect known and novel gene defects underlying retinal diseasesAudo, IsabelleBhattacharya, Shom ShankerZeitz, ChristinaNGSRetinal disordersDiagnostic toolThis is an Open Access article distributed under the terms of the Creative Commons Attribution License.-- et. al.[Background]: Inherited retinal disorders are clinically and genetically heterogeneous with more than 150 gene defects accounting for the diversity of disease phenotypes. So far, mutation detection was mainly performed by APEX technology and direct Sanger sequencing of known genes. However, these methods are time consuming, expensive and unable to provide a result if the patient carries a new gene mutation. In addition, multiplicity of phenotypes associated with the same gene defect may be overlooked.[Methods]: To overcome these challenges, we designed an exon sequencing array to target 254 known and candidate genes using Agilent capture. Subsequently, 20 DNA samples from 17 different families, including four patients with known mutations were sequenced using Illumina Genome Analyzer IIx next-generation-sequencing (NGS) platform. Different filtering approaches were applied to identify the genetic defect. The most likely disease causing variants were analyzed by Sanger sequencing. Co-segregation and sequencing analysis of control samples validated the pathogenicity of the observed variants.[Results]: The phenotype of the patients included retinitis pigmentosa, congenital stationary night blindness, Best disease, early-onset cone dystrophy and Stargardt disease. In three of four control samples with known genotypes NGS detected the expected mutations. Three known and five novel mutations were identified in NR2E3, PRPF3, EYS, PRPF8, CRB1, TRPM1 and CACNA1F. One of the control samples with a known genotype belongs to a family withtwo clinical phenotypes (Best and CSNB), where a novel mutation was identified for CSNB. In six families the disease associated mutations were not found, indicating that novel gene defects remain to be identified.The project was financially supported by GIS-maladies rares (CZ), Agence Nationale de la Recherche (ANR, SSB), Foundation Voir et Entendre and BQR, Foundation Fighting Blindness (IA, FFB Grant # CD-CL-0808-0466-CHNO and the CIC503 recognized as an FFB center, FFB Grant # C-CMM-0907-0428-INSERM04), Ville de Paris and region Ile de France.Peer reviewedBioMed CentralInstitut des Maladies Rares (France)Agence Nationale de la Recherche (France)Fondation Voir et EntendreFoundation Fighting BlindnessConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]201520152012info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/121645reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://dx.doi.org/10.1186/1750-1172-7-8Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/1216452026-05-22T06:33:51Z
dc.title.none.fl_str_mv Development and application of a next-generation-sequencing (NGS) approach to detect known and novel gene defects underlying retinal diseases
title Development and application of a next-generation-sequencing (NGS) approach to detect known and novel gene defects underlying retinal diseases
spellingShingle Development and application of a next-generation-sequencing (NGS) approach to detect known and novel gene defects underlying retinal diseases
Audo, Isabelle
NGS
Retinal disorders
Diagnostic tool
title_short Development and application of a next-generation-sequencing (NGS) approach to detect known and novel gene defects underlying retinal diseases
title_full Development and application of a next-generation-sequencing (NGS) approach to detect known and novel gene defects underlying retinal diseases
title_fullStr Development and application of a next-generation-sequencing (NGS) approach to detect known and novel gene defects underlying retinal diseases
title_full_unstemmed Development and application of a next-generation-sequencing (NGS) approach to detect known and novel gene defects underlying retinal diseases
title_sort Development and application of a next-generation-sequencing (NGS) approach to detect known and novel gene defects underlying retinal diseases
dc.creator.none.fl_str_mv Audo, Isabelle
Bhattacharya, Shom Shanker
Zeitz, Christina
author Audo, Isabelle
author_facet Audo, Isabelle
Bhattacharya, Shom Shanker
Zeitz, Christina
author_role author
author2 Bhattacharya, Shom Shanker
Zeitz, Christina
author2_role author
author
dc.contributor.none.fl_str_mv Institut des Maladies Rares (France)
Agence Nationale de la Recherche (France)
Fondation Voir et Entendre
Foundation Fighting Blindness
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv NGS
Retinal disorders
Diagnostic tool
topic NGS
Retinal disorders
Diagnostic tool
description This is an Open Access article distributed under the terms of the Creative Commons Attribution License.-- et. al.
publishDate 2012
dc.date.none.fl_str_mv 2012
2015
2015
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/121645
url http://hdl.handle.net/10261/121645
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://dx.doi.org/10.1186/1750-1172-7-8
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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