Assessment of a targeted resequencing assay as a support tool in the diagnosis of lysosomal storage disorders

Background: With over 50 different disorders and a combined incidence of up to 1/3000 births, lysosomal storage diseases (LSDs) constitute a major public health problem and place an enormous burden on affected individuals and their families. Many factors make LSD diagnosis difficult, including pheno...

Descripción completa

Detalles Bibliográficos
Autores: Fernández-Marmiesse A, Morey M, Pineda M, Eiris J, Couce ML, Castro-Gago M, Fraga JM, Lacerda L, Gouveia S, Pérez-Poyato MS, Armstrong J, Castiñeiras D, Cocho JA
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2014
País:España
Institución:Fundació Sant Joan de Déu
Repositorio:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
OAI Identifier:oai:fsjd.fundanetsuite.com:p6288
Acceso en línea:https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=6288
Access Level:acceso abierto
Palabra clave:In-solution enrichment
Targeted resequencing
Lysosomal storage disorders
Diagnostic odysseys
id ES_99ce68e95ca269a3f068efc116830f0d
oai_identifier_str oai:fsjd.fundanetsuite.com:p6288
network_acronym_str ES
network_name_str España
repository_id_str
spelling Assessment of a targeted resequencing assay as a support tool in the diagnosis of lysosomal storage disordersFernández-Marmiesse AMorey MPineda MEiris JCouce MLCastro-Gago MFraga JMLacerda LGouveia SPérez-Poyato MSArmstrong JCastiñeiras DCocho JAIn-solution enrichmentTargeted resequencingLysosomal storage disordersDiagnostic odysseysBackground: With over 50 different disorders and a combined incidence of up to 1/3000 births, lysosomal storage diseases (LSDs) constitute a major public health problem and place an enormous burden on affected individuals and their families. Many factors make LSD diagnosis difficult, including phenotype and penetrance variability, shared signs and symptoms, and problems inherent to biochemical diagnosis. Developing a powerful diagnostic tool could mitigate the protracted diagnostic process for these families, lead to better outcomes for current and proposed therapies, and provide the basis for more appropriate genetic counseling. Methods: We have designed a targeted resequencing assay for the simultaneous testing of 57 lysosomal genes, using in-solution capture as the enrichment method and two different sequencing platforms. A total of 84 patients with high to moderate-or low suspicion index for LSD were enrolled in different centers in Spain and Portugal, including 18 positive controls. Results: We correctly diagnosed 18 positive blinded controls, provided genetic diagnosis to 25 potential LSD patients, and ended with 18 diagnostic odysseys. Conclusion: We report the assessment of a next-generation-sequencing-based approach as an accessory tool in the diagnosis of LSDs, a group of disorders which have overlapping clinical profiles and genetic heterogeneity. We have also identified and quantified the strengths and limitations of next generation sequencing (NGS) technology applied to diagnosis.BMC2014info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=6288Orphanet Journal of Rare DiseasesISSN: 17501172reponame:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déuinstname:Fundació Sant Joan de DéuInglésinfo:eu-repo/semantics/openAccessoai:fsjd.fundanetsuite.com:p62882026-05-27T12:37:41Z
dc.title.none.fl_str_mv Assessment of a targeted resequencing assay as a support tool in the diagnosis of lysosomal storage disorders
title Assessment of a targeted resequencing assay as a support tool in the diagnosis of lysosomal storage disorders
spellingShingle Assessment of a targeted resequencing assay as a support tool in the diagnosis of lysosomal storage disorders
Fernández-Marmiesse A
In-solution enrichment
Targeted resequencing
Lysosomal storage disorders
Diagnostic odysseys
title_short Assessment of a targeted resequencing assay as a support tool in the diagnosis of lysosomal storage disorders
title_full Assessment of a targeted resequencing assay as a support tool in the diagnosis of lysosomal storage disorders
title_fullStr Assessment of a targeted resequencing assay as a support tool in the diagnosis of lysosomal storage disorders
title_full_unstemmed Assessment of a targeted resequencing assay as a support tool in the diagnosis of lysosomal storage disorders
title_sort Assessment of a targeted resequencing assay as a support tool in the diagnosis of lysosomal storage disorders
dc.creator.none.fl_str_mv Fernández-Marmiesse A
Morey M
Pineda M
Eiris J
Couce ML
Castro-Gago M
Fraga JM
Lacerda L
Gouveia S
Pérez-Poyato MS
Armstrong J
Castiñeiras D
Cocho JA
author Fernández-Marmiesse A
author_facet Fernández-Marmiesse A
Morey M
Pineda M
Eiris J
Couce ML
Castro-Gago M
Fraga JM
Lacerda L
Gouveia S
Pérez-Poyato MS
Armstrong J
Castiñeiras D
Cocho JA
author_role author
author2 Morey M
Pineda M
Eiris J
Couce ML
Castro-Gago M
Fraga JM
Lacerda L
Gouveia S
Pérez-Poyato MS
Armstrong J
Castiñeiras D
Cocho JA
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv In-solution enrichment
Targeted resequencing
Lysosomal storage disorders
Diagnostic odysseys
topic In-solution enrichment
Targeted resequencing
Lysosomal storage disorders
Diagnostic odysseys
description Background: With over 50 different disorders and a combined incidence of up to 1/3000 births, lysosomal storage diseases (LSDs) constitute a major public health problem and place an enormous burden on affected individuals and their families. Many factors make LSD diagnosis difficult, including phenotype and penetrance variability, shared signs and symptoms, and problems inherent to biochemical diagnosis. Developing a powerful diagnostic tool could mitigate the protracted diagnostic process for these families, lead to better outcomes for current and proposed therapies, and provide the basis for more appropriate genetic counseling. Methods: We have designed a targeted resequencing assay for the simultaneous testing of 57 lysosomal genes, using in-solution capture as the enrichment method and two different sequencing platforms. A total of 84 patients with high to moderate-or low suspicion index for LSD were enrolled in different centers in Spain and Portugal, including 18 positive controls. Results: We correctly diagnosed 18 positive blinded controls, provided genetic diagnosis to 25 potential LSD patients, and ended with 18 diagnostic odysseys. Conclusion: We report the assessment of a next-generation-sequencing-based approach as an accessory tool in the diagnosis of LSDs, a group of disorders which have overlapping clinical profiles and genetic heterogeneity. We have also identified and quantified the strengths and limitations of next generation sequencing (NGS) technology applied to diagnosis.
publishDate 2014
dc.date.none.fl_str_mv 2014
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=6288
url https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=6288
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv BMC
publisher.none.fl_str_mv BMC
dc.source.none.fl_str_mv Orphanet Journal of Rare Diseases
ISSN: 17501172
reponame:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
instname:Fundació Sant Joan de Déu
instname_str Fundació Sant Joan de Déu
reponame_str r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
collection r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869414319163179008
score 15.812429

Similares en LA Referencia