Diagnostic yield of next-generation sequencing in 87 families with neurodevelopmental disorders.

Background: Neurodevelopmental disorders (NDDs) are a group of heterogeneous conditions, which include mainly intellectual disability, developmental delay (DD) and autism spectrum disorder (ASD), among others. These diseases are highly heterogeneous and both genetic and environmental factors play an...

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Autores: Álvarez-Mora, María Isabel, Sánchez, Aurora, Rodríguez-Revenga Bodi, Laia, Corominas, Jordi, Rabionet Janssen, Raquel, Puig i Sardà, Susana, Madrigal, Irene
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
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:2445/186044
Acceso en línea:https://hdl.handle.net/2445/186044
Access Level:acceso abierto
Palabra clave:Trastorns del desenvolupament
Malalties hereditàries
Developmental disabilities
Genetic diseases
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spelling Diagnostic yield of next-generation sequencing in 87 families with neurodevelopmental disorders.Álvarez-Mora, María IsabelSánchez, AuroraRodríguez-Revenga Bodi, LaiaCorominas, JordiRabionet Janssen, RaquelPuig i Sardà, SusanaMadrigal, IreneTrastorns del desenvolupamentMalalties hereditàriesDevelopmental disabilitiesGenetic diseasesBackground: Neurodevelopmental disorders (NDDs) are a group of heterogeneous conditions, which include mainly intellectual disability, developmental delay (DD) and autism spectrum disorder (ASD), among others. These diseases are highly heterogeneous and both genetic and environmental factors play an important role in many of them. The introduction of next generation sequencing (NGS) has lead to the detection of genetic variants in several genetic diseases. The main aim of this report is to discuss the impact and advantages of the implementation of NGS in the diagnosis of NDDs. Herein, we report diagnostic yields of applying whole exome sequencing in 87 families afected by NDDs and additional data of whole genome sequencing (WGS) from 12 of these families. Results: The use of NGS technologies allowed identifying the causative gene alteration in approximately 36% (31/87) of the families. Among them, de novo mutation represented the most common cause of genetic alteration found in 48% (15/31) of the patients with diagnostic mutations. The majority of variants were located in known neurodevelop‑ mental disorders genes. Nevertheless, some of the diagnoses were made after the use of GeneMatcher tools which allow the identifcation of additional patients carrying mutations in THOC2, SETD1B and CHD9 genes. Finally the use of WGS only allowed the identifcation of disease causing variants in 8% (1/12) of the patients in which previous WES failed to identify a genetic aetiology. Conclusion: NGS is more powerful in identifying causative pathogenic variant than conventional algorithms based on chromosomal microarray as frst-tier test. Our results reinforce the implementation of NGS as a frst-test in genetic diagnosis of NDDs.BioMed Central2022202220222022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion10 p.application/pdfhttps://hdl.handle.net/2445/186044Articles 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)InglésReproducció del document publicat a: https://doi.org/10.1186/s13023-022-02213-zOrphanet Journal of Rare Diseases, 2022, vol. 17, num. 60, p. 1-10https://doi.org/10.1186/s13023-022-02213-zcc-by (c) Álvarez-Mora, María Isabel et al., 2022https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1860442026-05-29T05:05:01Z
dc.title.none.fl_str_mv Diagnostic yield of next-generation sequencing in 87 families with neurodevelopmental disorders.
title Diagnostic yield of next-generation sequencing in 87 families with neurodevelopmental disorders.
spellingShingle Diagnostic yield of next-generation sequencing in 87 families with neurodevelopmental disorders.
Álvarez-Mora, María Isabel
Trastorns del desenvolupament
Malalties hereditàries
Developmental disabilities
Genetic diseases
title_short Diagnostic yield of next-generation sequencing in 87 families with neurodevelopmental disorders.
title_full Diagnostic yield of next-generation sequencing in 87 families with neurodevelopmental disorders.
title_fullStr Diagnostic yield of next-generation sequencing in 87 families with neurodevelopmental disorders.
title_full_unstemmed Diagnostic yield of next-generation sequencing in 87 families with neurodevelopmental disorders.
title_sort Diagnostic yield of next-generation sequencing in 87 families with neurodevelopmental disorders.
dc.creator.none.fl_str_mv Álvarez-Mora, María Isabel
Sánchez, Aurora
Rodríguez-Revenga Bodi, Laia
Corominas, Jordi
Rabionet Janssen, Raquel
Puig i Sardà, Susana
Madrigal, Irene
author Álvarez-Mora, María Isabel
author_facet Álvarez-Mora, María Isabel
Sánchez, Aurora
Rodríguez-Revenga Bodi, Laia
Corominas, Jordi
Rabionet Janssen, Raquel
Puig i Sardà, Susana
Madrigal, Irene
author_role author
author2 Sánchez, Aurora
Rodríguez-Revenga Bodi, Laia
Corominas, Jordi
Rabionet Janssen, Raquel
Puig i Sardà, Susana
Madrigal, Irene
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Trastorns del desenvolupament
Malalties hereditàries
Developmental disabilities
Genetic diseases
topic Trastorns del desenvolupament
Malalties hereditàries
Developmental disabilities
Genetic diseases
description Background: Neurodevelopmental disorders (NDDs) are a group of heterogeneous conditions, which include mainly intellectual disability, developmental delay (DD) and autism spectrum disorder (ASD), among others. These diseases are highly heterogeneous and both genetic and environmental factors play an important role in many of them. The introduction of next generation sequencing (NGS) has lead to the detection of genetic variants in several genetic diseases. The main aim of this report is to discuss the impact and advantages of the implementation of NGS in the diagnosis of NDDs. Herein, we report diagnostic yields of applying whole exome sequencing in 87 families afected by NDDs and additional data of whole genome sequencing (WGS) from 12 of these families. Results: The use of NGS technologies allowed identifying the causative gene alteration in approximately 36% (31/87) of the families. Among them, de novo mutation represented the most common cause of genetic alteration found in 48% (15/31) of the patients with diagnostic mutations. The majority of variants were located in known neurodevelop‑ mental disorders genes. Nevertheless, some of the diagnoses were made after the use of GeneMatcher tools which allow the identifcation of additional patients carrying mutations in THOC2, SETD1B and CHD9 genes. Finally the use of WGS only allowed the identifcation of disease causing variants in 8% (1/12) of the patients in which previous WES failed to identify a genetic aetiology. Conclusion: NGS is more powerful in identifying causative pathogenic variant than conventional algorithms based on chromosomal microarray as frst-tier test. Our results reinforce the implementation of NGS as a frst-test in genetic diagnosis of NDDs.
publishDate 2022
dc.date.none.fl_str_mv 2022
2022
2022
2022
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://hdl.handle.net/2445/186044
url https://hdl.handle.net/2445/186044
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1186/s13023-022-02213-z
Orphanet Journal of Rare Diseases, 2022, vol. 17, num. 60, p. 1-10
https://doi.org/10.1186/s13023-022-02213-z
dc.rights.none.fl_str_mv cc-by (c) Álvarez-Mora, María Isabel et al., 2022
https://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Álvarez-Mora, María Isabel et al., 2022
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 10 p.
application/pdf
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
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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score 15,812455

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