Publicação
Phenotypic and functional consequences of haploinsufficiency of genes from exocyst and retinoic acid pathway due to a recurrent microdeletion of 2p13.2
| Resumo: | 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. |
|---|---|
| Autores principais: | Lopes, Fátima |
| Outros Autores: | Bessa, C.; Maciel, P. |
| Assunto: | 2p13 deletion EXOC6B CYP26B1 Developmental delay Cranial/skeletal anomalies |
| Ano: | 2013 |
| País: | Portugal |
| Tipo de documento: | artigo |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade do Minho |
| Idioma: | inglês |
| Origem: | RepositóriUM - Universidade do Minho |
| _version_ | 1867438754172502016 |
|---|---|
| author | Lopes, Fátima |
| author2 | Bessa, C. Maciel, P. |
| author2_role | author author |
| author_facet | Lopes, Fátima Bessa, C. Maciel, P. |
| author_role | author |
| contributor_name_str_mv | RepositóriUM - Universidade do Minho |
| country_str | PT |
| creators_json_txt | [{\"Person.name\":\"Lopes, Fátima\"},{\"Person.name\":\"Bessa, C.\"},{\"Person.name\":\"Maciel, P.\"}] |
| datacite.contributors.contributor.contributorName.fl_str_mv | RepositóriUM - Universidade do Minho |
| datacite.creators.creator.creatorName.fl_str_mv | Lopes, Fátima Bessa, C. Maciel, P. |
| datacite.date.Accepted.fl_str_mv | 2013-01-01T00:00:00Z |
| datacite.date.available.fl_str_mv | 2013-11-21T12:04:50Z |
| datacite.date.embargoed.fl_str_mv | 2013-11-21T12:04:50Z |
| datacite.rights.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| datacite.subjects.subject.fl_str_mv | 2p13 deletion EXOC6B CYP26B1 Developmental delay Cranial/skeletal anomalies |
| datacite.titles.title.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 |
| dc.contributor.none.fl_str_mv | RepositóriUM - Universidade do Minho |
| dc.creator.none.fl_str_mv | Lopes, Fátima Bessa, C. Maciel, P. |
| dc.date.Accepted.fl_str_mv | 2013-01-01T00:00:00Z |
| dc.date.available.fl_str_mv | 2013-11-21T12:04:50Z |
| dc.date.embargoed.fl_str_mv | 2013-11-21T12:04:50Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | https://hdl.handle.net/1822/26216 |
| dc.language.none.fl_str_mv | eng |
| dc.publisher.none.fl_str_mv | BioMed Central (BMC) |
| dc.rights.none.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| dc.subject.none.fl_str_mv | 2p13 deletion EXOC6B CYP26B1 Developmental delay Cranial/skeletal anomalies |
| dc.title.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 |
| dc.type.none.fl_str_mv | http://purl.org/coar/resource_type/c_6501 |
| description | 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. |
| dirty | 0 |
| eu_rights_str_mv | openAccess |
| format | article |
| fulltext.url.fl_str_mv | https://repositorium.uminho.pt/bitstreams/ae3a1c8b-82c7-47f4-ba64-e5af0505cf99/download |
| id | rum_06c8e2f37abaacd08d30a02166f3427f |
| identifier.url.fl_str_mv | https://hdl.handle.net/1822/26216 |
| instacron_str | repositorium |
| institution | Universidade do Minho |
| instname_str | Universidade do Minho |
| language | eng |
| network_acronym_str | rum |
| network_name_str | RepositóriUM - Universidade do Minho |
| oai_identifier_str | oai:repositorium.uminho.pt:1822/26216 |
| organization_str_mv | urn:organizationAcronym:repositorium |
| person_str_mv | Lopes, Fátima Bessa, C. Maciel, P. |
| publishDate | 2013 |
| publisher.none.fl_str_mv | BioMed Central (BMC) |
| reponame_str | RepositóriUM - Universidade do Minho |
| repository_id_str | urn:repositoryAcronym:rum |
| service_str_mv | urn:repositoryAcronym:rum |
| spelling | engBioMed Central (BMC)porRare, 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.application/pdfporPhenotypic and functional consequences of haploinsufficiency of genes from exocyst and retinoic acid pathway due to a recurrent microdeletion of 2p13.2Lopes, FátimaBessa, C.Maciel, P.HostingInstitutionOrganizationalRepositóriUM - Universidade do Minhoe-mailmailto:repositorium@usdb.uminho.ptrepositorium@usdb.uminho.ptPMID23837398ISSNIsPartOf1750-1172DOIIsPartOf10.1186/1750-1172-8-1002013-11-21T12:04:50Z20132013-10-31T16:29:03Z2013-01-01T00:00:00ZHandlehttps://hdl.handle.net/1822/26216http://purl.org/coar/access_right/c_abf2open access2p13 deletionEXOC6BCYP26B1Developmental delayCranial/skeletal anomalies1857721 bytesliteraturehttp://purl.org/coar/resource_type/c_6501journal articlehttp://purl.org/coar/access_right/c_abf2application/pdffulltexthttps://repositorium.uminho.pt/bitstreams/ae3a1c8b-82c7-47f4-ba64-e5af0505cf99/download |
| 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 |
| status | SINGLETON |
| subject.fl_str_mv | 2p13 deletion EXOC6B CYP26B1 Developmental delay Cranial/skeletal anomalies |
| title | 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_short | 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 |
| topic | 2p13 deletion EXOC6B CYP26B1 Developmental delay Cranial/skeletal anomalies |
| topic_facet | 2p13 deletion EXOC6B CYP26B1 Developmental delay Cranial/skeletal anomalies |
| url | https://hdl.handle.net/1822/26216 |
| visible | 1 |