Targeted next generation sequencing identifies novel pathogenic variants and provides molecular diagnoses in a cohort of pediatric and adult patients with unexplained mitochondrial dysfunction

Detalhes bibliográficos
Autor(a) principal: Nogueira, Célia
Data de Publicação: 2019
Outros Autores: Silva, Lisbeth, Pereira, Cristina, Vieira, Luís, Leão Teles, Elisa, Rodrigues, Esmeralda, Campos, Teresa, Janeiro, Patrícia, Gaspar, Ana, Dupont, Juliette, Bandeira, Anabela, Martins, Esmeralda, Magalhães, Marina, Sequeira, Sílvia, Vieira, José Pedro, Santos, Helena, Vilarinho, Sílvia, Vilarinho, Laura
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10400.18/6560
Resumo: Mitochondrial diseases (MD) are a group of rare inherited disorders, characterized by phenotypic heterogeneity, with hitherto no effective therapeutic options. The aim of this study was to develop a next generation sequencing (NGS) strategy, by using a custom gene panel and whole mitochondrial genome, to identify the disease causing pathogenic variants in 146 patients suspicious of MD. The molecular analysis of this cohort revealed six novel and 15 described pathogenic variants, as well as 26 variants of unknown significance. Our findings are expanding the mutational landscape of these disorders and support the use of a NGS strategy for a higher diagnostic yield.
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spelling Targeted next generation sequencing identifies novel pathogenic variants and provides molecular diagnoses in a cohort of pediatric and adult patients with unexplained mitochondrial dysfunctionMitochondrial DiseasesGene PanelmtDNANuclear GenesNext Generation SequencingRespiratory ChainDoenças GenéticasMitochondrial diseases (MD) are a group of rare inherited disorders, characterized by phenotypic heterogeneity, with hitherto no effective therapeutic options. The aim of this study was to develop a next generation sequencing (NGS) strategy, by using a custom gene panel and whole mitochondrial genome, to identify the disease causing pathogenic variants in 146 patients suspicious of MD. The molecular analysis of this cohort revealed six novel and 15 described pathogenic variants, as well as 26 variants of unknown significance. Our findings are expanding the mutational landscape of these disorders and support the use of a NGS strategy for a higher diagnostic yield.This work was supported by FCT (PTDC/DTP-PIC/2220/2014) and NORTE2020 (NORTE-01-0246-FEDER-000014). Silvia Vilarinho is supported by the National Institute Of Diabetes And Digestive And Kidney Diseases of the National Institutes of Health under Award Number K08DK113109. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.Elsevier/ Mitochondria Research SocietyRepositório Científico do Instituto Nacional de SaúdeNogueira, CéliaSilva, LisbethPereira, CristinaVieira, LuísLeão Teles, ElisaRodrigues, EsmeraldaCampos, TeresaJaneiro, PatríciaGaspar, AnaDupont, JulietteBandeira, AnabelaMartins, EsmeraldaMagalhães, MarinaSequeira, SílviaVieira, José PedroSantos, HelenaVilarinho, SílviaVilarinho, Laura2020-04-30T17:30:01Z2019-03-012019-03-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.18/6560engMitochondrion. 2019 Jul;47:309-317. doi: 10.1016/j.mito.2019.02.006. Epub 2019 Mar 11567-724910.1016/j.mito.2019.02.006info:eu-repo/semantics/embargoedAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-20T15:41:23Zoai:repositorio.insa.pt:10400.18/6560Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:41:00.996219Repositório 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 Targeted next generation sequencing identifies novel pathogenic variants and provides molecular diagnoses in a cohort of pediatric and adult patients with unexplained mitochondrial dysfunction
title Targeted next generation sequencing identifies novel pathogenic variants and provides molecular diagnoses in a cohort of pediatric and adult patients with unexplained mitochondrial dysfunction
spellingShingle Targeted next generation sequencing identifies novel pathogenic variants and provides molecular diagnoses in a cohort of pediatric and adult patients with unexplained mitochondrial dysfunction
Nogueira, Célia
Mitochondrial Diseases
Gene Panel
mtDNA
Nuclear Genes
Next Generation Sequencing
Respiratory Chain
Doenças Genéticas
title_short Targeted next generation sequencing identifies novel pathogenic variants and provides molecular diagnoses in a cohort of pediatric and adult patients with unexplained mitochondrial dysfunction
title_full Targeted next generation sequencing identifies novel pathogenic variants and provides molecular diagnoses in a cohort of pediatric and adult patients with unexplained mitochondrial dysfunction
title_fullStr Targeted next generation sequencing identifies novel pathogenic variants and provides molecular diagnoses in a cohort of pediatric and adult patients with unexplained mitochondrial dysfunction
title_full_unstemmed Targeted next generation sequencing identifies novel pathogenic variants and provides molecular diagnoses in a cohort of pediatric and adult patients with unexplained mitochondrial dysfunction
title_sort Targeted next generation sequencing identifies novel pathogenic variants and provides molecular diagnoses in a cohort of pediatric and adult patients with unexplained mitochondrial dysfunction
author Nogueira, Célia
author_facet Nogueira, Célia
Silva, Lisbeth
Pereira, Cristina
Vieira, Luís
Leão Teles, Elisa
Rodrigues, Esmeralda
Campos, Teresa
Janeiro, Patrícia
Gaspar, Ana
Dupont, Juliette
Bandeira, Anabela
Martins, Esmeralda
Magalhães, Marina
Sequeira, Sílvia
Vieira, José Pedro
Santos, Helena
Vilarinho, Sílvia
Vilarinho, Laura
author_role author
author2 Silva, Lisbeth
Pereira, Cristina
Vieira, Luís
Leão Teles, Elisa
Rodrigues, Esmeralda
Campos, Teresa
Janeiro, Patrícia
Gaspar, Ana
Dupont, Juliette
Bandeira, Anabela
Martins, Esmeralda
Magalhães, Marina
Sequeira, Sílvia
Vieira, José Pedro
Santos, Helena
Vilarinho, Sílvia
Vilarinho, Laura
author2_role 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 Instituto Nacional de Saúde
dc.contributor.author.fl_str_mv Nogueira, Célia
Silva, Lisbeth
Pereira, Cristina
Vieira, Luís
Leão Teles, Elisa
Rodrigues, Esmeralda
Campos, Teresa
Janeiro, Patrícia
Gaspar, Ana
Dupont, Juliette
Bandeira, Anabela
Martins, Esmeralda
Magalhães, Marina
Sequeira, Sílvia
Vieira, José Pedro
Santos, Helena
Vilarinho, Sílvia
Vilarinho, Laura
dc.subject.por.fl_str_mv Mitochondrial Diseases
Gene Panel
mtDNA
Nuclear Genes
Next Generation Sequencing
Respiratory Chain
Doenças Genéticas
topic Mitochondrial Diseases
Gene Panel
mtDNA
Nuclear Genes
Next Generation Sequencing
Respiratory Chain
Doenças Genéticas
description Mitochondrial diseases (MD) are a group of rare inherited disorders, characterized by phenotypic heterogeneity, with hitherto no effective therapeutic options. The aim of this study was to develop a next generation sequencing (NGS) strategy, by using a custom gene panel and whole mitochondrial genome, to identify the disease causing pathogenic variants in 146 patients suspicious of MD. The molecular analysis of this cohort revealed six novel and 15 described pathogenic variants, as well as 26 variants of unknown significance. Our findings are expanding the mutational landscape of these disorders and support the use of a NGS strategy for a higher diagnostic yield.
publishDate 2019
dc.date.none.fl_str_mv 2019-03-01
2019-03-01T00:00:00Z
2020-04-30T17:30:01Z
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/10400.18/6560
url http://hdl.handle.net/10400.18/6560
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Mitochondrion. 2019 Jul;47:309-317. doi: 10.1016/j.mito.2019.02.006. Epub 2019 Mar 1
1567-7249
10.1016/j.mito.2019.02.006
dc.rights.driver.fl_str_mv info:eu-repo/semantics/embargoedAccess
eu_rights_str_mv embargoedAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier/ Mitochondria Research Society
publisher.none.fl_str_mv Elsevier/ Mitochondria Research Society
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection 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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