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

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
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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
Fil: Teres Rodrigo, Maria. Universidad de Zaragoza; España
Fil: Eckhold, Juliane. Universität zu Lübeck; Alemania
Fil: Puisac, Beatriz. Universidad de Zaragoza; España
Fil: Dalski, Andreas. Universität zu Lübeck; Alemania
Fil: Gil Rodriguez, Maria C.. Universidad de Zaragoza; España
Fil: Braunholz, Diana. Universität zu Lübeck; Alemania
Fil: Baquero, Carolina. Universidad de Zaragoza; España. Hospital Pablo Tobon Uribe. Medellin; Colombia
Fil: Hernández Marcos, Maria. Universidad de Zaragoza; España
Fil: de Karam, Juan C.. Universidad de Zaragoza; España
Fil: Ciero, Milagros. Universidad de Zaragoza; España
Fil: Santos Simarro, Fernando. Hospital Universitario La Paz. Madrid; España
Fil: Lapunzina, Pablo. Hospital Universitario La Paz. Madrid; España
Fil: Wierzba, Jolanta. University of Gdańsk; Polonia
Fil: 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; Argentina
Fil: Ramos, Feliciano J.. Universidad de Zaragoza; España. University Clinic Hospital "Lozano Blesa"; España
Fil: Gillessen Kaesbach, Gabriele. Universität zu Lübeck; Alemania
Fil: Kaiser, Frank. Universität zu Lübeck; Alemania
Fil: Pie, Juan. Universidad de Zaragoza; España
Materia
CdLS
NIPBL
splicing mutations
physiological splicing
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/34104
Acceder
id CONICETDig_dfa6475a3abcb0326e0afd3ff2a80e2d
oai_identifier_str oai:ri.conicet.gov.ar:11336/34104
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
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 Técnicas2025-09-29T10:21:56Zoai: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:34982025-09-29 10:21:56.56CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
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
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
topic CdLS
NIPBL
splicing mutations
physiological splicing
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv 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
Fil: Teres Rodrigo, Maria. Universidad de Zaragoza; España
Fil: Eckhold, Juliane. Universität zu Lübeck; Alemania
Fil: Puisac, Beatriz. Universidad de Zaragoza; España
Fil: Dalski, Andreas. Universität zu Lübeck; Alemania
Fil: Gil Rodriguez, Maria C.. Universidad de Zaragoza; España
Fil: Braunholz, Diana. Universität zu Lübeck; Alemania
Fil: Baquero, Carolina. Universidad de Zaragoza; España. Hospital Pablo Tobon Uribe. Medellin; Colombia
Fil: Hernández Marcos, Maria. Universidad de Zaragoza; España
Fil: de Karam, Juan C.. Universidad de Zaragoza; España
Fil: Ciero, Milagros. Universidad de Zaragoza; España
Fil: Santos Simarro, Fernando. Hospital Universitario La Paz. Madrid; España
Fil: Lapunzina, Pablo. Hospital Universitario La Paz. Madrid; España
Fil: Wierzba, Jolanta. University of Gdańsk; Polonia
Fil: 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; Argentina
Fil: Ramos, Feliciano J.. Universidad de Zaragoza; España. University Clinic Hospital "Lozano Blesa"; España
Fil: Gillessen Kaesbach, Gabriele. Universität zu Lübeck; Alemania
Fil: Kaiser, Frank. Universität zu Lübeck; Alemania
Fil: Pie, Juan. Universidad de Zaragoza; España
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
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
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
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score 13.070432

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