mRNA Quantification of NIPBL Isoforms A and B in Adult and Fetal Human Tissues, and a Potentially Pathological Variant Affecting Only Isoform A in Two Patients with Cornelia de Lange Syndrome

Cornelia de Lange syndrome (CdLS) is a congenital developmental disorder characterized by craniofacial dysmorphia, growth retardation, limb malformations, and intellectual disability. Approximately 60% of patients with CdLS carry a recognizable pathological variant in the <i>NIPBL</i> ge...

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Autores: Puisac, Beatriz, Teresa-Rodrigo, María-Esperanza, Hernández-Marcos, María, Baquero-Montoya, Carolina, Gil-Rodríguez, María Concepción, Visnes, Torkild, Bot, Christopher, Gómez-Puertas, Paulino, Kaiser, Frank J., Ramos, Feliciano J., Ström, Lena, Pié, Juan
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2017
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/149366
Acceso en línea:http://hdl.handle.net/10261/149366
Access Level:acceso abierto
Palabra clave:Cornelia de Lange syndrome
NIPBL pathological variant
Splicing variants
mRNA
Adult tissues
Fetal tissues
NIPBL isoform A
NIPBL isoform B
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spelling mRNA Quantification of NIPBL Isoforms A and B in Adult and Fetal Human Tissues, and a Potentially Pathological Variant Affecting Only Isoform A in Two Patients with Cornelia de Lange SyndromePuisac, BeatrizTeresa-Rodrigo, María-EsperanzaHernández-Marcos, MaríaBaquero-Montoya, CarolinaGil-Rodríguez, María ConcepciónVisnes, TorkildBot, ChristopherGómez-Puertas, PaulinoKaiser, Frank J.Ramos, Feliciano J.Ström, LenaPié, JuanCornelia de Lange syndromeNIPBL pathological variantSplicing variantsmRNAAdult tissuesFetal tissuesNIPBL isoform ANIPBL isoform BCornelia de Lange syndrome (CdLS) is a congenital developmental disorder characterized by craniofacial dysmorphia, growth retardation, limb malformations, and intellectual disability. Approximately 60% of patients with CdLS carry a recognizable pathological variant in the <i>NIPBL</i> gene, of which two isoforms, A and B, have been identified, and which only differ in the C-terminal segment. In this work, we describe the distribution pattern of the isoforms A and B mRNAs in tissues of adult and fetal origin, by qPCR (quantitative polymerase chain reaction). Our results show a higher gene expression of the isoform A, even though both seem to have the same tissue distribution. Interestingly, the expression in fetal tissues is higher than that of adults, especially in brain and skeletal muscle. Curiously, the study of fibroblasts of two siblings with a mild CdLS phenotype and a pathological variant specific of the isoform A of <i>NIPBL</i> (c.8387A > G; P.Tyr2796Cys), showed a similar reduction in both isoforms, and a normal sensitivity to DNA damage. Overall, these results suggest that the position of the pathological variant at the 3´ end of the <i>NIPBL</i> gene affecting only isoform A, is likely to be the cause of the atypical mild phenotype of the two brothers.We sincerely thank the patients’ family for participating in this study. This work was supported by: The Spanish Ministry of Health—Fondo de Investigación Sanitaria (FIS) (Ref: PI15/00707); the Diputación General de Aragón (Grupo Consolidado B20), European Social Fund (“Construyendo Europa desde Aragón”) CHROMATIN-Net funded by the German Federal Ministry of Education and Research (BMBF) to Frank J. Kaiser. The Spanish Ministry of Economy (Refs: IPT2011-0964-900000 and SAF2011-13156-E) to Paulino Gómez-Puertas. Swedish Research Council to Lena Ström and the Norwegian Research Council (205217) to Torkild Visnes Beatriz Puisac, María Hernández-Marcos, María-Esperanza Teresa-Rodrigo, María-Concepción Gil-Rodríguez, Feliciano J. Ramos and Juan Pié are members of CIBERER-GCV02 and ISS-Aragon at the School of Medicine, University of Zaragoza and the Hospital Clínico Universitario “Lozano Blesa”.We acknowledge support by the CSIC Open Access Publication Initiative through its Unit of Information Resources for Research (URICI).Multidisciplinary Digital Publishing InstituteConsejo Superior de Investigaciones Científicas (España)Ministerio de Sanidad y Consumo (España)Diputación General de AragónFederal Ministry of Education and Research (Germany)European CommissionMinisterio de Economía y Competitividad (España)Swedish Research CouncilNorwegian Research CouncilConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2017201720172017info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/149366reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttps://doi.org/10.3390/ijms18030481Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/1493662026-05-22T06:33:51Z
dc.title.none.fl_str_mv mRNA Quantification of NIPBL Isoforms A and B in Adult and Fetal Human Tissues, and a Potentially Pathological Variant Affecting Only Isoform A in Two Patients with Cornelia de Lange Syndrome
title mRNA Quantification of NIPBL Isoforms A and B in Adult and Fetal Human Tissues, and a Potentially Pathological Variant Affecting Only Isoform A in Two Patients with Cornelia de Lange Syndrome
spellingShingle mRNA Quantification of NIPBL Isoforms A and B in Adult and Fetal Human Tissues, and a Potentially Pathological Variant Affecting Only Isoform A in Two Patients with Cornelia de Lange Syndrome
Puisac, Beatriz
Cornelia de Lange syndrome
NIPBL pathological variant
Splicing variants
mRNA
Adult tissues
Fetal tissues
NIPBL isoform A
NIPBL isoform B
title_short mRNA Quantification of NIPBL Isoforms A and B in Adult and Fetal Human Tissues, and a Potentially Pathological Variant Affecting Only Isoform A in Two Patients with Cornelia de Lange Syndrome
title_full mRNA Quantification of NIPBL Isoforms A and B in Adult and Fetal Human Tissues, and a Potentially Pathological Variant Affecting Only Isoform A in Two Patients with Cornelia de Lange Syndrome
title_fullStr mRNA Quantification of NIPBL Isoforms A and B in Adult and Fetal Human Tissues, and a Potentially Pathological Variant Affecting Only Isoform A in Two Patients with Cornelia de Lange Syndrome
title_full_unstemmed mRNA Quantification of NIPBL Isoforms A and B in Adult and Fetal Human Tissues, and a Potentially Pathological Variant Affecting Only Isoform A in Two Patients with Cornelia de Lange Syndrome
title_sort mRNA Quantification of NIPBL Isoforms A and B in Adult and Fetal Human Tissues, and a Potentially Pathological Variant Affecting Only Isoform A in Two Patients with Cornelia de Lange Syndrome
dc.creator.none.fl_str_mv Puisac, Beatriz
Teresa-Rodrigo, María-Esperanza
Hernández-Marcos, María
Baquero-Montoya, Carolina
Gil-Rodríguez, María Concepción
Visnes, Torkild
Bot, Christopher
Gómez-Puertas, Paulino
Kaiser, Frank J.
Ramos, Feliciano J.
Ström, Lena
Pié, Juan
author Puisac, Beatriz
author_facet Puisac, Beatriz
Teresa-Rodrigo, María-Esperanza
Hernández-Marcos, María
Baquero-Montoya, Carolina
Gil-Rodríguez, María Concepción
Visnes, Torkild
Bot, Christopher
Gómez-Puertas, Paulino
Kaiser, Frank J.
Ramos, Feliciano J.
Ström, Lena
Pié, Juan
author_role author
author2 Teresa-Rodrigo, María-Esperanza
Hernández-Marcos, María
Baquero-Montoya, Carolina
Gil-Rodríguez, María Concepción
Visnes, Torkild
Bot, Christopher
Gómez-Puertas, Paulino
Kaiser, Frank J.
Ramos, Feliciano J.
Ström, Lena
Pié, Juan
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Consejo Superior de Investigaciones Científicas (España)
Ministerio de Sanidad y Consumo (España)
Diputación General de Aragón
Federal Ministry of Education and Research (Germany)
European Commission
Ministerio de Economía y Competitividad (España)
Swedish Research Council
Norwegian Research Council
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Cornelia de Lange syndrome
NIPBL pathological variant
Splicing variants
mRNA
Adult tissues
Fetal tissues
NIPBL isoform A
NIPBL isoform B
topic Cornelia de Lange syndrome
NIPBL pathological variant
Splicing variants
mRNA
Adult tissues
Fetal tissues
NIPBL isoform A
NIPBL isoform B
description Cornelia de Lange syndrome (CdLS) is a congenital developmental disorder characterized by craniofacial dysmorphia, growth retardation, limb malformations, and intellectual disability. Approximately 60% of patients with CdLS carry a recognizable pathological variant in the <i>NIPBL</i> gene, of which two isoforms, A and B, have been identified, and which only differ in the C-terminal segment. In this work, we describe the distribution pattern of the isoforms A and B mRNAs in tissues of adult and fetal origin, by qPCR (quantitative polymerase chain reaction). Our results show a higher gene expression of the isoform A, even though both seem to have the same tissue distribution. Interestingly, the expression in fetal tissues is higher than that of adults, especially in brain and skeletal muscle. Curiously, the study of fibroblasts of two siblings with a mild CdLS phenotype and a pathological variant specific of the isoform A of <i>NIPBL</i> (c.8387A > G; P.Tyr2796Cys), showed a similar reduction in both isoforms, and a normal sensitivity to DNA damage. Overall, these results suggest that the position of the pathological variant at the 3´ end of the <i>NIPBL</i> gene affecting only isoform A, is likely to be the cause of the atypical mild phenotype of the two brothers.
publishDate 2017
dc.date.none.fl_str_mv 2017
2017
2017
2017
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/149366
url http://hdl.handle.net/10261/149366
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv https://doi.org/10.3390/ijms18030481
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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