Phenotypic and functional consequences of haploinsufficiency of genes from exocyst and retinoic acid pathway due to a recurrent microdeletion of 2p13.2

Detalhes bibliográficos
Autor(a) principal: Lopes, Fátima
Data de Publicação: 2013
Outros Autores: Bessa, C., Maciel, P.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/1822/26216
Resumo: Phenotypic and functional consequences of haploinsufficiency of genes from exocyst and retinoic acid pathway due to a recurrent microdeletion of 2p13.2.
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spelling Phenotypic and functional consequences of haploinsufficiency of genes from exocyst and retinoic acid pathway due to a recurrent microdeletion of 2p13.22p13 deletionEXOC6BCYP26B1Developmental delayCranial/skeletal anomaliesScience & TechnologyPhenotypic and functional consequences of haploinsufficiency of genes from exocyst and retinoic acid pathway due to a recurrent microdeletion of 2p13.2.Rare, recurrent genomic imbalances facilitate the association of genotype with abnormalities at the "whole body" level. However, at the cellular level, the functional consequences of recurrent genomic abnormalities and how they can be linked to the phenotype are much less investigated. METHOD AND RESULTS: We report an example of a functional analysis of two genes from a new, overlapping microdeletion of 2p13.2 region (from 72,140,702-72,924,626). The subjects shared intellectual disability (ID), language delay, hyperactivity, facial asymmetry, ear malformations, and vertebral and/or craniofacial abnormalities. The overlapping region included two genes, EXOC6B and CYP26B1, which are involved in exocytosis/Notch signaling and retinoic acid (RA) metabolism, respectively, and are of critical importance for early morphogenesis, symmetry as well as craniofacial, skeleton and brain development. The abnormal function of EXOC6B was documented in patient lymphoblasts by its reduced expression and with perturbed expression of Notch signaling pathway genes HES1 and RBPJ, previously noted to be the consequence of EXOC6B dysfunction in animal and cell line models. Similarly, the function of CYP26B1 was affected by the deletion since the retinoic acid induced expression of this gene in patient lymphoblasts was significantly lower compared to controls (8% of controls). CONCLUSION: Haploinsufficiency of CYP26B1 and EXOC6B genes involved in retinoic acid and exocyst/Notch signaling pathways, respectively, has not been reported previously in humans. The developmental anomalies and phenotypic features of our subjects are in keeping with the dysfunction of these genes, considering their known role. Documenting their dysfunction at the cellular level in patient cells enhanced our understanding of biological processes which contribute to the clinical phenotype.We would like to sincerely acknowledge the families of the presented cases for participation in the genetic studies and for allowing this publication. This work was supported by funding from the Canadian Institutes for Health Research (CIHR) (RT-64217; PI: MESL and MOP 74502; PI: ERS), Autism Speaks (PI: MESL) and Fundacao para a Ciencia e Tecnologia (PIC/IC/83026/2007. MES and ERS are Career Investigators with the Michael Smith Foundation for Health Research. The experiments were supported in part by a US National institutes of Health grant R01 GM081569 (NI and CN).BioMed Central (BMC)Universidade do MinhoLopes, FátimaBessa, C.Maciel, P.20132013-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/26216eng1750-117210.1186/1750-1172-8-10023837398info: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:RCAAP2023-07-21T12:22:38Zoai:repositorium.sdum.uminho.pt:1822/26216Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:16:10.212291Repositório 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 Phenotypic and functional consequences of haploinsufficiency of genes from exocyst and retinoic acid pathway due to a recurrent microdeletion of 2p13.2
title Phenotypic and functional consequences of haploinsufficiency of genes from exocyst and retinoic acid pathway due to a recurrent microdeletion of 2p13.2
spellingShingle Phenotypic and functional consequences of haploinsufficiency of genes from exocyst and retinoic acid pathway due to a recurrent microdeletion of 2p13.2
Lopes, Fátima
2p13 deletion
EXOC6B
CYP26B1
Developmental delay
Cranial/skeletal anomalies
Science & Technology
title_short Phenotypic and functional consequences of haploinsufficiency of genes from exocyst and retinoic acid pathway due to a recurrent microdeletion of 2p13.2
title_full Phenotypic and functional consequences of haploinsufficiency of genes from exocyst and retinoic acid pathway due to a recurrent microdeletion of 2p13.2
title_fullStr Phenotypic and functional consequences of haploinsufficiency of genes from exocyst and retinoic acid pathway due to a recurrent microdeletion of 2p13.2
title_full_unstemmed Phenotypic and functional consequences of haploinsufficiency of genes from exocyst and retinoic acid pathway due to a recurrent microdeletion of 2p13.2
title_sort Phenotypic and functional consequences of haploinsufficiency of genes from exocyst and retinoic acid pathway due to a recurrent microdeletion of 2p13.2
author Lopes, Fátima
author_facet Lopes, Fátima
Bessa, C.
Maciel, P.
author_role author
author2 Bessa, C.
Maciel, P.
author2_role author
author
dc.contributor.none.fl_str_mv Universidade do Minho
dc.contributor.author.fl_str_mv Lopes, Fátima
Bessa, C.
Maciel, P.
dc.subject.por.fl_str_mv 2p13 deletion
EXOC6B
CYP26B1
Developmental delay
Cranial/skeletal anomalies
Science & Technology
topic 2p13 deletion
EXOC6B
CYP26B1
Developmental delay
Cranial/skeletal anomalies
Science & Technology
description Phenotypic and functional consequences of haploinsufficiency of genes from exocyst and retinoic acid pathway due to a recurrent microdeletion of 2p13.2.
publishDate 2013
dc.date.none.fl_str_mv 2013
2013-01-01T00:00:00Z
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/1822/26216
url http://hdl.handle.net/1822/26216
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 1750-1172
10.1186/1750-1172-8-100
23837398
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 BioMed Central (BMC)
publisher.none.fl_str_mv BioMed Central (BMC)
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
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