Genomic imbalances defining novel intellectual disability associated loci
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Outros Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.16/2428 |
Resumo: | Background: High resolution genome-wide copy number analysis, routinely used in clinical diagnosis for several years, retrieves new and extremely rare copy number variations (CNVs) that provide novel candidate genes contributing to disease etiology. The aim of this work was to identify novel genetic causes of neurodevelopmental disease, inferred from CNVs detected by array comparative hybridization (aCGH), in a cohort of 325 Portuguese patients with intellectual disability (ID). Results: We have detected CNVs in 30.1% of the patients, of which 5.2% corresponded to novel likely pathogenic CNVs. For these 11 rare CNVs (which encompass novel ID candidate genes), we identified those most likely to be relevant, and established genotype-phenotype correlations based on detailed clinical assessment. In the case of duplications, we performed expression analysis to assess the impact of the rearrangement. Interestingly, these novel candidate genes belong to known ID-related pathways. Within the 8% of patients with CNVs in known pathogenic loci, the majority had a clinical presentation fitting the phenotype(s) described in the literature, with a few interesting exceptions that are discussed. Conclusions: Identification of such rare CNVs (some of which reported for the first time in ID patients/families) contributes to our understanding of the etiology of ID and for the ever-improving diagnosis of this group of patients. |
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Genomic imbalances defining novel intellectual disability associated lociCNVsNeurodevelopmentGenotype-phenotype correlationCUL4B overexpressionBackground: High resolution genome-wide copy number analysis, routinely used in clinical diagnosis for several years, retrieves new and extremely rare copy number variations (CNVs) that provide novel candidate genes contributing to disease etiology. The aim of this work was to identify novel genetic causes of neurodevelopmental disease, inferred from CNVs detected by array comparative hybridization (aCGH), in a cohort of 325 Portuguese patients with intellectual disability (ID). Results: We have detected CNVs in 30.1% of the patients, of which 5.2% corresponded to novel likely pathogenic CNVs. For these 11 rare CNVs (which encompass novel ID candidate genes), we identified those most likely to be relevant, and established genotype-phenotype correlations based on detailed clinical assessment. In the case of duplications, we performed expression analysis to assess the impact of the rearrangement. Interestingly, these novel candidate genes belong to known ID-related pathways. Within the 8% of patients with CNVs in known pathogenic loci, the majority had a clinical presentation fitting the phenotype(s) described in the literature, with a few interesting exceptions that are discussed. Conclusions: Identification of such rare CNVs (some of which reported for the first time in ID patients/families) contributes to our understanding of the etiology of ID and for the ever-improving diagnosis of this group of patients.This work has been funded by FEDER funds, through the Competitiveness Factors Operational Programme (COMPETE), and by National funds, through the Foundation for Science and Technology (FCT), under the scope of the projects: PIC/IC/83026/2007, PIC/IC/83013/2007 and POCI-01-0145-FEDER-007038. This work has also been funded by the project NORTE-01-0145-FEDER-000013, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER). FL was supported by Foundation for Science and Technology (FCT) through the fellowship SFRH/BD/90167/2012BMCRepositório Científico do Centro Hospitalar Universitário de Santo AntónioLopes, FátimaTorres, FátimaSoares, GabrielaBarbosa, MafaldaSilva, JoãoDuque, FredericoRocha, MiguelSá, JoaquimOliveira, GuiomarSá, Maria JoãoTemudo, TeresaSousa, SusanaMarques, CarlaLopes, SofiaGomes, CatarinaBarros, GiselaJorge, ArmindaRocha, FelisbelaMartins, CecíliaMesquita, SandraLoureiro, SusanaCardoso, Elisa MariaCálix, Maria JoséDias, AndreiaMartins, CristinaMota, Céu RAntunes, DianaDupont, JulietteFigueiredo, SaraFigueiroa, SóniaGama-de-Sousa, SusanaCruz, SaraSampaio, AdrianaEijk, PaulWeiss, Marjan MYlstra, BaukeRendeiro, PaulaTavares, PurificaçãoReis-Lima, MargaridaPinto-Basto, JorgeFortuna, Ana MariaMaciel, Patrícia2020-07-14T15:02:40Z20192019-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.16/2428engLopes F, Torres F, Soares G, et al. Genomic imbalances defining novel intellectual disability associated loci. Orphanet J Rare Dis. 2019;14(1):164. Published 2019 Jul 5. doi:10.1186/s13023-019-1135-01750-117210.1186/s13023-019-1135-0info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-10-20T11:00:40Zoai:repositorio.chporto.pt:10400.16/2428Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:38:37.478231Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Genomic imbalances defining novel intellectual disability associated loci |
title |
Genomic imbalances defining novel intellectual disability associated loci |
spellingShingle |
Genomic imbalances defining novel intellectual disability associated loci Lopes, Fátima CNVs Neurodevelopment Genotype-phenotype correlation CUL4B overexpression |
title_short |
Genomic imbalances defining novel intellectual disability associated loci |
title_full |
Genomic imbalances defining novel intellectual disability associated loci |
title_fullStr |
Genomic imbalances defining novel intellectual disability associated loci |
title_full_unstemmed |
Genomic imbalances defining novel intellectual disability associated loci |
title_sort |
Genomic imbalances defining novel intellectual disability associated loci |
author |
Lopes, Fátima |
author_facet |
Lopes, Fátima Torres, Fátima Soares, Gabriela Barbosa, Mafalda Silva, João Duque, Frederico Rocha, Miguel Sá, Joaquim Oliveira, Guiomar Sá, Maria João Temudo, Teresa Sousa, Susana Marques, Carla Lopes, Sofia Gomes, Catarina Barros, Gisela Jorge, Arminda Rocha, Felisbela Martins, Cecília Mesquita, Sandra Loureiro, Susana Cardoso, Elisa Maria Cálix, Maria José Dias, Andreia Martins, Cristina Mota, Céu R Antunes, Diana Dupont, Juliette Figueiredo, Sara Figueiroa, Sónia Gama-de-Sousa, Susana Cruz, Sara Sampaio, Adriana Eijk, Paul Weiss, Marjan M Ylstra, Bauke Rendeiro, Paula Tavares, Purificação Reis-Lima, Margarida Pinto-Basto, Jorge Fortuna, Ana Maria Maciel, Patrícia |
author_role |
author |
author2 |
Torres, Fátima Soares, Gabriela Barbosa, Mafalda Silva, João Duque, Frederico Rocha, Miguel Sá, Joaquim Oliveira, Guiomar Sá, Maria João Temudo, Teresa Sousa, Susana Marques, Carla Lopes, Sofia Gomes, Catarina Barros, Gisela Jorge, Arminda Rocha, Felisbela Martins, Cecília Mesquita, Sandra Loureiro, Susana Cardoso, Elisa Maria Cálix, Maria José Dias, Andreia Martins, Cristina Mota, Céu R Antunes, Diana Dupont, Juliette Figueiredo, Sara Figueiroa, Sónia Gama-de-Sousa, Susana Cruz, Sara Sampaio, Adriana Eijk, Paul Weiss, Marjan M Ylstra, Bauke Rendeiro, Paula Tavares, Purificação Reis-Lima, Margarida Pinto-Basto, Jorge Fortuna, Ana Maria Maciel, Patrícia |
author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Repositório Científico do Centro Hospitalar Universitário de Santo António |
dc.contributor.author.fl_str_mv |
Lopes, Fátima Torres, Fátima Soares, Gabriela Barbosa, Mafalda Silva, João Duque, Frederico Rocha, Miguel Sá, Joaquim Oliveira, Guiomar Sá, Maria João Temudo, Teresa Sousa, Susana Marques, Carla Lopes, Sofia Gomes, Catarina Barros, Gisela Jorge, Arminda Rocha, Felisbela Martins, Cecília Mesquita, Sandra Loureiro, Susana Cardoso, Elisa Maria Cálix, Maria José Dias, Andreia Martins, Cristina Mota, Céu R Antunes, Diana Dupont, Juliette Figueiredo, Sara Figueiroa, Sónia Gama-de-Sousa, Susana Cruz, Sara Sampaio, Adriana Eijk, Paul Weiss, Marjan M Ylstra, Bauke Rendeiro, Paula Tavares, Purificação Reis-Lima, Margarida Pinto-Basto, Jorge Fortuna, Ana Maria Maciel, Patrícia |
dc.subject.por.fl_str_mv |
CNVs Neurodevelopment Genotype-phenotype correlation CUL4B overexpression |
topic |
CNVs Neurodevelopment Genotype-phenotype correlation CUL4B overexpression |
description |
Background: High resolution genome-wide copy number analysis, routinely used in clinical diagnosis for several years, retrieves new and extremely rare copy number variations (CNVs) that provide novel candidate genes contributing to disease etiology. The aim of this work was to identify novel genetic causes of neurodevelopmental disease, inferred from CNVs detected by array comparative hybridization (aCGH), in a cohort of 325 Portuguese patients with intellectual disability (ID). Results: We have detected CNVs in 30.1% of the patients, of which 5.2% corresponded to novel likely pathogenic CNVs. For these 11 rare CNVs (which encompass novel ID candidate genes), we identified those most likely to be relevant, and established genotype-phenotype correlations based on detailed clinical assessment. In the case of duplications, we performed expression analysis to assess the impact of the rearrangement. Interestingly, these novel candidate genes belong to known ID-related pathways. Within the 8% of patients with CNVs in known pathogenic loci, the majority had a clinical presentation fitting the phenotype(s) described in the literature, with a few interesting exceptions that are discussed. Conclusions: Identification of such rare CNVs (some of which reported for the first time in ID patients/families) contributes to our understanding of the etiology of ID and for the ever-improving diagnosis of this group of patients. |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019 2019-01-01T00:00:00Z 2020-07-14T15:02:40Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10400.16/2428 |
url |
http://hdl.handle.net/10400.16/2428 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Lopes F, Torres F, Soares G, et al. Genomic imbalances defining novel intellectual disability associated loci. Orphanet J Rare Dis. 2019;14(1):164. Published 2019 Jul 5. doi:10.1186/s13023-019-1135-0 1750-1172 10.1186/s13023-019-1135-0 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
BMC |
publisher.none.fl_str_mv |
BMC |
dc.source.none.fl_str_mv |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
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1799133647094153216 |