Molecular diagnosis of patients with epilepsy and developmental delay using a customized panel of epilepsy genes

Pediatric epilepsies are a group of disorders with a broad phenotypic spectrum that are associated with great genetic heterogeneity, thus making sequential single-gene testing an impractical basis for diagnostic strategy. The advent of next-generation sequencing has increased the success rate of epi...

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Autores: Ortega-Moreno, Laura, Giráldez, Beatriz G., Soto Insuga, Víctor, Losada-del Pozo, Rebeca, Rodrigo-Moreno, María, Alarcón-Morcillo, Cristina, Sánchez Martín, Gema, Díaz-Gómez, Esther, Guerrero-López, Rosa, Serratosa Fernández, José María, Grupo Español de Genética de las Epilepsias de la Infancia (GEGEI)
Tipo de recurso: artículo
Fecha de publicación:2017
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/681188
Acceso en línea:http://hdl.handle.net/10486/681188
https://dx.doi.org/10.1371/journal.pone.0188978
Access Level:acceso abierto
Palabra clave:Pediatric epilepsies
Genetic panels
Epilepsy diagnosis
Developmental delay
Genes
Patients
Medicina
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spelling Molecular diagnosis of patients with epilepsy and developmental delay using a customized panel of epilepsy genesOrtega-Moreno, LauraGiráldez, Beatriz G.Soto Insuga, VíctorLosada-del Pozo, RebecaRodrigo-Moreno, MaríaAlarcón-Morcillo, CristinaSánchez Martín, GemaDíaz-Gómez, EstherGuerrero-López, RosaSerratosa Fernández, José MaríaGrupo Español de Genética de las Epilepsias de la Infancia (GEGEI)Pediatric epilepsiesGenetic panelsEpilepsy diagnosisDevelopmental delayGenesPatientsMedicinaPediatric epilepsies are a group of disorders with a broad phenotypic spectrum that are associated with great genetic heterogeneity, thus making sequential single-gene testing an impractical basis for diagnostic strategy. The advent of next-generation sequencing has increased the success rate of epilepsy diagnosis, and targeted resequencing using genetic panels is the a most cost-effective choice. We report the results found in a group of 87 patients with epilepsy and developmental delay using targeted next generation sequencing (custom-designed Haloplex panel). Using this gene panel, we were able to identify disease-causing variants in 17 out of 87 (19.5%) analyzed patients, all found in known epilepsy-associated genes (KCNQ2, CDKL5, STXBP1, SCN1A, PCDH19, POLG, SLC2A1, ARX, ALG13, CHD2, SYNGAP1, and GRIN1). Twelve of 18 variants arose de novo and 6 were novel. The highest yield was found in patients with onset in the first years of life, especially in patients classified as having early-onset epileptic encephalopathy. Knowledge of the underlying genetic cause provides essential information on prognosis and could be used to avoid unnecessary studies, which may result in a greater diagnostic cost-effectiveness.This work was supported by the Ministerio de Economía y Competitividad (SAF2010-18586 and SAF2013-48960-P) to GSM, LOM (www.mineco.gob.es); Fundación Conchita Rábago de Jiménez Díaz (www.fundacionconchitarabago.net) to LOM and Centro de Investigación Biomédica en Red de Enfermedades Raras (www.ciberer.es) to RGL.Public Library of ScienceDepartamento de MedicinaFacultad de MedicinaInstituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD)20172017-11-30research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/681188https://dx.doi.org/10.1371/journal.pone.0188978reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/6811882026-06-23T12:46:27Z
dc.title.none.fl_str_mv Molecular diagnosis of patients with epilepsy and developmental delay using a customized panel of epilepsy genes
title Molecular diagnosis of patients with epilepsy and developmental delay using a customized panel of epilepsy genes
spellingShingle Molecular diagnosis of patients with epilepsy and developmental delay using a customized panel of epilepsy genes
Ortega-Moreno, Laura
Pediatric epilepsies
Genetic panels
Epilepsy diagnosis
Developmental delay
Genes
Patients
Medicina
title_short Molecular diagnosis of patients with epilepsy and developmental delay using a customized panel of epilepsy genes
title_full Molecular diagnosis of patients with epilepsy and developmental delay using a customized panel of epilepsy genes
title_fullStr Molecular diagnosis of patients with epilepsy and developmental delay using a customized panel of epilepsy genes
title_full_unstemmed Molecular diagnosis of patients with epilepsy and developmental delay using a customized panel of epilepsy genes
title_sort Molecular diagnosis of patients with epilepsy and developmental delay using a customized panel of epilepsy genes
dc.creator.none.fl_str_mv Ortega-Moreno, Laura
Giráldez, Beatriz G.
Soto Insuga, Víctor
Losada-del Pozo, Rebeca
Rodrigo-Moreno, María
Alarcón-Morcillo, Cristina
Sánchez Martín, Gema
Díaz-Gómez, Esther
Guerrero-López, Rosa
Serratosa Fernández, José María
Grupo Español de Genética de las Epilepsias de la Infancia (GEGEI)
author Ortega-Moreno, Laura
author_facet Ortega-Moreno, Laura
Giráldez, Beatriz G.
Soto Insuga, Víctor
Losada-del Pozo, Rebeca
Rodrigo-Moreno, María
Alarcón-Morcillo, Cristina
Sánchez Martín, Gema
Díaz-Gómez, Esther
Guerrero-López, Rosa
Serratosa Fernández, José María
Grupo Español de Genética de las Epilepsias de la Infancia (GEGEI)
author_role author
author2 Giráldez, Beatriz G.
Soto Insuga, Víctor
Losada-del Pozo, Rebeca
Rodrigo-Moreno, María
Alarcón-Morcillo, Cristina
Sánchez Martín, Gema
Díaz-Gómez, Esther
Guerrero-López, Rosa
Serratosa Fernández, José María
Grupo Español de Genética de las Epilepsias de la Infancia (GEGEI)
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Departamento de Medicina
Facultad de Medicina
Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD)
dc.subject.none.fl_str_mv Pediatric epilepsies
Genetic panels
Epilepsy diagnosis
Developmental delay
Genes
Patients
Medicina
topic Pediatric epilepsies
Genetic panels
Epilepsy diagnosis
Developmental delay
Genes
Patients
Medicina
description Pediatric epilepsies are a group of disorders with a broad phenotypic spectrum that are associated with great genetic heterogeneity, thus making sequential single-gene testing an impractical basis for diagnostic strategy. The advent of next-generation sequencing has increased the success rate of epilepsy diagnosis, and targeted resequencing using genetic panels is the a most cost-effective choice. We report the results found in a group of 87 patients with epilepsy and developmental delay using targeted next generation sequencing (custom-designed Haloplex panel). Using this gene panel, we were able to identify disease-causing variants in 17 out of 87 (19.5%) analyzed patients, all found in known epilepsy-associated genes (KCNQ2, CDKL5, STXBP1, SCN1A, PCDH19, POLG, SLC2A1, ARX, ALG13, CHD2, SYNGAP1, and GRIN1). Twelve of 18 variants arose de novo and 6 were novel. The highest yield was found in patients with onset in the first years of life, especially in patients classified as having early-onset epileptic encephalopathy. Knowledge of the underlying genetic cause provides essential information on prognosis and could be used to avoid unnecessary studies, which may result in a greater diagnostic cost-effectiveness.
publishDate 2017
dc.date.none.fl_str_mv 2017
2017-11-30
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10486/681188
https://dx.doi.org/10.1371/journal.pone.0188978
url http://hdl.handle.net/10486/681188
https://dx.doi.org/10.1371/journal.pone.0188978
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
dc.source.none.fl_str_mv reponame:Biblos-e Archivo. Repositorio Institucional de la UAM
instname:Universidad Autónoma de Madrid
instname_str Universidad Autónoma de Madrid
reponame_str Biblos-e Archivo. Repositorio Institucional de la UAM
collection Biblos-e Archivo. Repositorio Institucional de la UAM
repository.name.fl_str_mv
repository.mail.fl_str_mv
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