Functional Characterization of NIPBL Physiological Splice Variants and Eight Splicing Mutations in Patients with Cornelia de Lange Syndrome

Cornelia de Lange syndrome (CdLS) is a congenital developmental disorder characterized by distinctive craniofacial features, growth retardation, cognitive impairment, limb defects, hirsutism, and multisystem involvement. Mutations in five genes encoding structural components (SMC1A, SMC3, RAD21) or...

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Autores: Teres Rodrigo, Maria, Eckhold, Juliane, Puisac, Beatriz, Dalski, Andreas, Gil Rodriguez, Maria C., Braunholz, Diana, Baquero, Carolina, Hernández Marcos, Maria, de Karam, Juan C., Ciero, Milagros, Santos Simarro, Fernando, Lapunzina, Pablo, Wierzba, Jolanta, Casale, Cesar Horacio, Ramos, Feliciano J., Gillessen Kaesbach, Gabriele, Kaiser, Frank, Pie, Juan
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2014
País:Argentina
Recursos:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/34104
Acesso em linha:http://hdl.handle.net/11336/34104
Access Level:acceso abierto
Palavra-chave:CdLS
NIPBL
splicing mutations
physiological splicing
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
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network_acronym_str AR
network_name_str Argentina
repository_id_str
dc.title.none.fl_str_mv Functional Characterization of NIPBL Physiological Splice Variants and Eight Splicing Mutations in Patients with Cornelia de Lange Syndrome
title Functional Characterization of NIPBL Physiological Splice Variants and Eight Splicing Mutations in Patients with Cornelia de Lange Syndrome
spellingShingle Functional Characterization of NIPBL Physiological Splice Variants and Eight Splicing Mutations in Patients with Cornelia de Lange Syndrome
Teres Rodrigo, Maria
CdLS
NIPBL
splicing mutations
physiological splicing
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
title_short Functional Characterization of NIPBL Physiological Splice Variants and Eight Splicing Mutations in Patients with Cornelia de Lange Syndrome
title_full Functional Characterization of NIPBL Physiological Splice Variants and Eight Splicing Mutations in Patients with Cornelia de Lange Syndrome
title_fullStr Functional Characterization of NIPBL Physiological Splice Variants and Eight Splicing Mutations in Patients with Cornelia de Lange Syndrome
title_full_unstemmed Functional Characterization of NIPBL Physiological Splice Variants and Eight Splicing Mutations in Patients with Cornelia de Lange Syndrome
title_sort Functional Characterization of NIPBL Physiological Splice Variants and Eight Splicing Mutations in Patients with Cornelia de Lange Syndrome
dc.creator.none.fl_str_mv Teres Rodrigo, Maria
Eckhold, Juliane
Puisac, Beatriz
Dalski, Andreas
Gil Rodriguez, Maria C.
Braunholz, Diana
Baquero, Carolina
Hernández Marcos, Maria
de Karam, Juan C.
Ciero, Milagros
Santos Simarro, Fernando
Lapunzina, Pablo
Wierzba, Jolanta
Casale, Cesar Horacio
Ramos, Feliciano J.
Gillessen Kaesbach, Gabriele
Kaiser, Frank
Pie, Juan
author Teres Rodrigo, Maria
author_facet Teres Rodrigo, Maria
Eckhold, Juliane
Puisac, Beatriz
Dalski, Andreas
Gil Rodriguez, Maria C.
Braunholz, Diana
Baquero, Carolina
Hernández Marcos, Maria
de Karam, Juan C.
Ciero, Milagros
Santos Simarro, Fernando
Lapunzina, Pablo
Wierzba, Jolanta
Casale, Cesar Horacio
Ramos, Feliciano J.
Gillessen Kaesbach, Gabriele
Kaiser, Frank
Pie, Juan
author_role author
author2 Eckhold, Juliane
Puisac, Beatriz
Dalski, Andreas
Gil Rodriguez, Maria C.
Braunholz, Diana
Baquero, Carolina
Hernández Marcos, Maria
de Karam, Juan C.
Ciero, Milagros
Santos Simarro, Fernando
Lapunzina, Pablo
Wierzba, Jolanta
Casale, Cesar Horacio
Ramos, Feliciano J.
Gillessen Kaesbach, Gabriele
Kaiser, Frank
Pie, Juan
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv CdLS
NIPBL
splicing mutations
physiological splicing
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
topic CdLS
NIPBL
splicing mutations
physiological splicing
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
description Cornelia de Lange syndrome (CdLS) is a congenital developmental disorder characterized by distinctive craniofacial features, growth retardation, cognitive impairment, limb defects, hirsutism, and multisystem involvement. Mutations in five genes encoding structural components (SMC1A, SMC3, RAD21) or functionally associated factors (NIPBL, HDAC8) of the cohesin complex have been found in patients with CdLS. In about 60% of the patients, mutations in NIPBL could be identified. Interestingly, 17% of them are predicted to change normal splicing, however, detailed molecular investigations are often missing. Here, we report the first systematic study of the physiological splicing of the NIPBL gene, that would reveal the identification of four new splicing isoforms ΔE10, ΔE12, ΔE33,34, and B’. Furthermore, we have investigated nine mutations affecting splice-sites in the NIPBL gene identified in twelve CdLS patients. All mutations have been examined on the DNA and RNA level, as well as by in silico analyses. Although patients with mutations affecting NIPBL splicing show a broad clinical variability, the more severe phenotypes seem to be associated with aberrant transcripts resulting in a shift of the reading frame. View Full-Text
publishDate 2014
dc.date.none.fl_str_mv 2014-05
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/34104
Teres Rodrigo, Maria; Eckhold, Juliane; Puisac, Beatriz; Dalski, Andreas; Gil Rodriguez, Maria C.; et al.; Functional Characterization of NIPBL Physiological Splice Variants and Eight Splicing Mutations in Patients with Cornelia de Lange Syndrome; Molecular Diversity Preservation International; International Journal of Molecular Sciences; 15; 6; 5-2014; 10350-10364
1422-0067
CONICET Digital
CONICET
url http://hdl.handle.net/11336/34104
identifier_str_mv Teres Rodrigo, Maria; Eckhold, Juliane; Puisac, Beatriz; Dalski, Andreas; Gil Rodriguez, Maria C.; et al.; Functional Characterization of NIPBL Physiological Splice Variants and Eight Splicing Mutations in Patients with Cornelia de Lange Syndrome; Molecular Diversity Preservation International; International Journal of Molecular Sciences; 15; 6; 5-2014; 10350-10364
1422-0067
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/ 10.3390/ijms150610350
info:eu-repo/semantics/altIdentifier/url/http://www.mdpi.com/1422-0067/15/6/10350
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Molecular Diversity Preservation International
publisher.none.fl_str_mv Molecular Diversity Preservation International
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1799195967752241152
spelling Functional Characterization of NIPBL Physiological Splice Variants and Eight Splicing Mutations in Patients with Cornelia de Lange SyndromeTeres Rodrigo, MariaEckhold, JulianePuisac, BeatrizDalski, AndreasGil Rodriguez, Maria C.Braunholz, DianaBaquero, CarolinaHernández Marcos, Mariade Karam, Juan C.Ciero, MilagrosSantos Simarro, FernandoLapunzina, PabloWierzba, JolantaCasale, Cesar HoracioRamos, Feliciano J.Gillessen Kaesbach, GabrieleKaiser, FrankPie, JuanCdLSNIPBLsplicing mutationsphysiological splicinghttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Cornelia de Lange syndrome (CdLS) is a congenital developmental disorder characterized by distinctive craniofacial features, growth retardation, cognitive impairment, limb defects, hirsutism, and multisystem involvement. Mutations in five genes encoding structural components (SMC1A, SMC3, RAD21) or functionally associated factors (NIPBL, HDAC8) of the cohesin complex have been found in patients with CdLS. In about 60% of the patients, mutations in NIPBL could be identified. Interestingly, 17% of them are predicted to change normal splicing, however, detailed molecular investigations are often missing. Here, we report the first systematic study of the physiological splicing of the NIPBL gene, that would reveal the identification of four new splicing isoforms ΔE10, ΔE12, ΔE33,34, and B’. Furthermore, we have investigated nine mutations affecting splice-sites in the NIPBL gene identified in twelve CdLS patients. All mutations have been examined on the DNA and RNA level, as well as by in silico analyses. Although patients with mutations affecting NIPBL splicing show a broad clinical variability, the more severe phenotypes seem to be associated with aberrant transcripts resulting in a shift of the reading frame. View Full-TextFil: Teres Rodrigo, Maria. Universidad de Zaragoza; EspañaFil: Eckhold, Juliane. Universität zu Lübeck; AlemaniaFil: Puisac, Beatriz. Universidad de Zaragoza; EspañaFil: Dalski, Andreas. Universität zu Lübeck; AlemaniaFil: Gil Rodriguez, Maria C.. Universidad de Zaragoza; EspañaFil: Braunholz, Diana. Universität zu Lübeck; AlemaniaFil: Baquero, Carolina. Universidad de Zaragoza; España. Hospital Pablo Tobon Uribe. Medellin; ColombiaFil: Hernández Marcos, Maria. Universidad de Zaragoza; EspañaFil: de Karam, Juan C.. Universidad de Zaragoza; EspañaFil: Ciero, Milagros. Universidad de Zaragoza; EspañaFil: Santos Simarro, Fernando. Hospital Universitario La Paz. Madrid; EspañaFil: Lapunzina, Pablo. Hospital Universitario La Paz. Madrid; EspañaFil: Wierzba, Jolanta. University of Gdańsk; PoloniaFil: Casale, Cesar Horacio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Departamento de Biología Molecular; ArgentinaFil: Ramos, Feliciano J.. Universidad de Zaragoza; España. University Clinic Hospital "Lozano Blesa"; EspañaFil: Gillessen Kaesbach, Gabriele. Universität zu Lübeck; AlemaniaFil: Kaiser, Frank. Universität zu Lübeck; AlemaniaFil: Pie, Juan. Universidad de Zaragoza; EspañaMolecular Diversity Preservation International2014-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/34104Teres Rodrigo, Maria; Eckhold, Juliane; Puisac, Beatriz; Dalski, Andreas; Gil Rodriguez, Maria C.; et al.; Functional Characterization of NIPBL Physiological Splice Variants and Eight Splicing Mutations in Patients with Cornelia de Lange Syndrome; Molecular Diversity Preservation International; International Journal of Molecular Sciences; 15; 6; 5-2014; 10350-103641422-0067CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/ 10.3390/ijms150610350info:eu-repo/semantics/altIdentifier/url/http://www.mdpi.com/1422-0067/15/6/10350info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2024-05-08T14:10:07Zoai:ri.conicet.gov.ar:11336/34104instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982024-05-08 14:10:07.719CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
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