The role of AKT3 copy number changes in brain abnormalities and neurodevelopmental disorders: four new cases and literature review
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/10400.18/6607 |
Resumo: | Microdeletions at 1q43-q44 have been described as resulting in a clinically recognizable phenotype of intellectual disability (ID), facial dysmorphisms and microcephaly (MIC). In contrast, the reciprocal microduplications of 1q43-q44 region have been less frequently reported and patients showed a variable phenotype, including macrocephaly. Reports of a large number of patients with copy number variations involving this region highlighted the AKT3 gene as a likely key player in head size anomalies. We report four novel patients with copy number variations in the 1q43-q44 region: one with a larger deletion (3.7Mb), two with smaller deletions affecting AKT3 and SDCCAG8 genes (0.16 and 0.18Mb) and one with a quadruplication (1Mb) that affects the entire AKT3 gene. All patients with deletions presented MIC without structural brain abnormalities, whereas the patient with quadruplication had macrocephaly, but his carrier father had normal head circumference. Our report also includes a comparison of phenotypes in cases with 1q43-q44 duplications to assist future genotype-phenotype correlations. Our observations implicate AKT3 as a contributor to ID/development delay (DD) and head size but raise doubts about its straightforward impact on the latter aspect of the phenotype in patients with 1q43-q44 deletion/duplication syndrome. |
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The role of AKT3 copy number changes in brain abnormalities and neurodevelopmental disorders: four new cases and literature review1q43-q44 CNVsAKT3SDCCAG8ZBTB18MacrocephalyMicrocephalyPhenotypic ExpressivityDoenças GenéticasMicrodeletions at 1q43-q44 have been described as resulting in a clinically recognizable phenotype of intellectual disability (ID), facial dysmorphisms and microcephaly (MIC). In contrast, the reciprocal microduplications of 1q43-q44 region have been less frequently reported and patients showed a variable phenotype, including macrocephaly. Reports of a large number of patients with copy number variations involving this region highlighted the AKT3 gene as a likely key player in head size anomalies. We report four novel patients with copy number variations in the 1q43-q44 region: one with a larger deletion (3.7Mb), two with smaller deletions affecting AKT3 and SDCCAG8 genes (0.16 and 0.18Mb) and one with a quadruplication (1Mb) that affects the entire AKT3 gene. All patients with deletions presented MIC without structural brain abnormalities, whereas the patient with quadruplication had macrocephaly, but his carrier father had normal head circumference. Our report also includes a comparison of phenotypes in cases with 1q43-q44 duplications to assist future genotype-phenotype correlations. Our observations implicate AKT3 as a contributor to ID/development delay (DD) and head size but raise doubts about its straightforward impact on the latter aspect of the phenotype in patients with 1q43-q44 deletion/duplication syndrome.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. The 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/90167/2012.Frontiers MediaRepositório Científico do Instituto Nacional de SaúdeLopes, FátimaTorres, FátimaSoares, Gabrielavan Karnebeek, Clara D.Martins, CecíliaAntunes, DianaSilva, JoãoMuttucomaroe, LaurenBotelho, Luís FilipeSousa, SusanaRendeiro, PaulaTavares, PurificaçãoVan Esch, HildeRajcan-Separovic, EvicaMaciel, Patrícia2020-05-06T16:43:36Z2019-02-222019-02-22T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.18/6607engFront Genet. 2019 Feb 22;10:58. doi: 10.3389/fgene.2019.00058. eCollection 2019.1664-802110.3389/fgene.2019.00058info: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:RCAAP2023-07-20T15:41:45Zoai:repositorio.insa.pt:10400.18/6607Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:41:41.265193Repositório 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 |
The role of AKT3 copy number changes in brain abnormalities and neurodevelopmental disorders: four new cases and literature review |
title |
The role of AKT3 copy number changes in brain abnormalities and neurodevelopmental disorders: four new cases and literature review |
spellingShingle |
The role of AKT3 copy number changes in brain abnormalities and neurodevelopmental disorders: four new cases and literature review Lopes, Fátima 1q43-q44 CNVs AKT3 SDCCAG8 ZBTB18 Macrocephaly Microcephaly Phenotypic Expressivity Doenças Genéticas |
title_short |
The role of AKT3 copy number changes in brain abnormalities and neurodevelopmental disorders: four new cases and literature review |
title_full |
The role of AKT3 copy number changes in brain abnormalities and neurodevelopmental disorders: four new cases and literature review |
title_fullStr |
The role of AKT3 copy number changes in brain abnormalities and neurodevelopmental disorders: four new cases and literature review |
title_full_unstemmed |
The role of AKT3 copy number changes in brain abnormalities and neurodevelopmental disorders: four new cases and literature review |
title_sort |
The role of AKT3 copy number changes in brain abnormalities and neurodevelopmental disorders: four new cases and literature review |
author |
Lopes, Fátima |
author_facet |
Lopes, Fátima Torres, Fátima Soares, Gabriela van Karnebeek, Clara D. Martins, Cecília Antunes, Diana Silva, João Muttucomaroe, Lauren Botelho, Luís Filipe Sousa, Susana Rendeiro, Paula Tavares, Purificação Van Esch, Hilde Rajcan-Separovic, Evica Maciel, Patrícia |
author_role |
author |
author2 |
Torres, Fátima Soares, Gabriela van Karnebeek, Clara D. Martins, Cecília Antunes, Diana Silva, João Muttucomaroe, Lauren Botelho, Luís Filipe Sousa, Susana Rendeiro, Paula Tavares, Purificação Van Esch, Hilde Rajcan-Separovic, Evica Maciel, Patrícia |
author2_role |
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 |
Lopes, Fátima Torres, Fátima Soares, Gabriela van Karnebeek, Clara D. Martins, Cecília Antunes, Diana Silva, João Muttucomaroe, Lauren Botelho, Luís Filipe Sousa, Susana Rendeiro, Paula Tavares, Purificação Van Esch, Hilde Rajcan-Separovic, Evica Maciel, Patrícia |
dc.subject.por.fl_str_mv |
1q43-q44 CNVs AKT3 SDCCAG8 ZBTB18 Macrocephaly Microcephaly Phenotypic Expressivity Doenças Genéticas |
topic |
1q43-q44 CNVs AKT3 SDCCAG8 ZBTB18 Macrocephaly Microcephaly Phenotypic Expressivity Doenças Genéticas |
description |
Microdeletions at 1q43-q44 have been described as resulting in a clinically recognizable phenotype of intellectual disability (ID), facial dysmorphisms and microcephaly (MIC). In contrast, the reciprocal microduplications of 1q43-q44 region have been less frequently reported and patients showed a variable phenotype, including macrocephaly. Reports of a large number of patients with copy number variations involving this region highlighted the AKT3 gene as a likely key player in head size anomalies. We report four novel patients with copy number variations in the 1q43-q44 region: one with a larger deletion (3.7Mb), two with smaller deletions affecting AKT3 and SDCCAG8 genes (0.16 and 0.18Mb) and one with a quadruplication (1Mb) that affects the entire AKT3 gene. All patients with deletions presented MIC without structural brain abnormalities, whereas the patient with quadruplication had macrocephaly, but his carrier father had normal head circumference. Our report also includes a comparison of phenotypes in cases with 1q43-q44 duplications to assist future genotype-phenotype correlations. Our observations implicate AKT3 as a contributor to ID/development delay (DD) and head size but raise doubts about its straightforward impact on the latter aspect of the phenotype in patients with 1q43-q44 deletion/duplication syndrome. |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019-02-22 2019-02-22T00:00:00Z 2020-05-06T16:43:36Z |
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/10400.18/6607 |
url |
http://hdl.handle.net/10400.18/6607 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Front Genet. 2019 Feb 22;10:58. doi: 10.3389/fgene.2019.00058. eCollection 2019. 1664-8021 10.3389/fgene.2019.00058 |
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 |
Frontiers Media |
publisher.none.fl_str_mv |
Frontiers Media |
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) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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