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 / Carolina Baquero Montoya    

Público ISBD Título : 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 Tipo de documento : documento electrónico Autores : Carolina Baquero Montoya, Fecha de publicación : 2017 Títulos uniformes : International Journal of Molecular Sciences Dimensiones : PDF Idioma : Inglés (eng) Palabras clave : Cornelia de Lange syndrome  NIPBL isoform A  NIPBL isoform B  NIPBL pathological variant  adult tissues  fetal tissues  mRNA  splicing variants Resumen : 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 NIPBL 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 NIPBL (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 NIPBL gene affecting only isoform A, is likely to be the cause of the atypical mild phenotype of the two brothers. Mención de responsabilidad : Beatriz Puisac, María-Esperanza Teresa-Rodrigo, María Hernández-Marcos, Carolina Baquero-Montoya, María-Concepción Gil-Rodríguez, Torkild Visnes, Christopher Bot, Paulino Gómez-Puertas, Frank J Kaiser, Feliciano J Ramos, Lena Ström, Juan Pié Referencia : Int J Mol Sci. 2017 Feb 23;18(3). pii: E481 DOI (Digital Object Identifier) : 10.3390/ijms18030481 PMID : 28241484 Derechos de uso : CC BY En línea : https://www.mdpi.com/1422-0067/18/3/481 Enlace permanente : https://hospitalpablotobon.cloudbiteca.com/pmb/opac_css/index.php?lvl=notice_display&id=3419 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 [documento electrónico] / Carolina Baquero Montoya,  . - 2017 . -  ; PDF. Obra : International Journal of Molecular Sciences Idioma : Inglés (eng) Palabras clave : Cornelia de Lange syndrome  NIPBL isoform A  NIPBL isoform B  NIPBL pathological variant  adult tissues  fetal tissues  mRNA  splicing variants Resumen : 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 NIPBL 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 NIPBL (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 NIPBL gene affecting only isoform A, is likely to be the cause of the atypical mild phenotype of the two brothers. Mención de responsabilidad : Beatriz Puisac, María-Esperanza Teresa-Rodrigo, María Hernández-Marcos, Carolina Baquero-Montoya, María-Concepción Gil-Rodríguez, Torkild Visnes, Christopher Bot, Paulino Gómez-Puertas, Frank J Kaiser, Feliciano J Ramos, Lena Ström, Juan Pié Referencia : Int J Mol Sci. 2017 Feb 23;18(3). pii: E481 DOI (Digital Object Identifier) : 10.3390/ijms18030481 PMID : 28241484 Derechos de uso : CC BY En línea : https://www.mdpi.com/1422-0067/18/3/481 Enlace permanente : https://hospitalpablotobon.cloudbiteca.com/pmb/opac_css/index.php?lvl=notice_display&id=3419

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Functional characterization of NIPBL physiological splice variants and eight splicing mutations in patients with Cornelia de Lange syndrome / Carolina Baquero Montoya    

Público ISBD Título : Functional characterization of NIPBL physiological splice variants and eight splicing mutations in patients with Cornelia de Lange syndrome Tipo de documento : documento electrónico Autores : Carolina Baquero Montoya, Fecha de publicación : 2014 Títulos uniformes : International Journal of Molecular Sciences Idioma : Inglés (eng) Palabras clave : CdLS  NIPBL  splicing mutations  physiological splicing Resumen : 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. Mención de responsabilidad : María E Teresa-Rodrigo, Juliane Eckhold, Beatriz Puisac, Andreas Dalski, María C Gil-Rodríguez, Diana Braunholz, Carolina Baquero, María Hernández-Marcos, Juan C de Karam, Milagros Ciero, Fernando Santos-Simarro, Pablo Lapunzina, Jolanta Wierzba, César H Casale, Feliciano J Ramos, Gabriele Gillessen-Kaesbach, Frank J Kaiser, Juan Pié Referencia : Int J Mol Sci. 2014 Jun 10;15(6):10350-64. DOI (Digital Object Identifier) : 10.3390/ijms150610350 PMID : 24918291 Derechos de uso : CC BY En línea : https://www.mdpi.com/1422-0067/15/6/10350 Enlace permanente : https://hospitalpablotobon.cloudbiteca.com/pmb/opac_css/index.php?lvl=notice_display&id=3782 Functional characterization of NIPBL physiological splice variants and eight splicing mutations in patients with Cornelia de Lange syndrome [documento electrónico] / Carolina Baquero Montoya,  . - 2014. Obra : International Journal of Molecular Sciences Idioma : Inglés (eng) Palabras clave : CdLS  NIPBL  splicing mutations  physiological splicing Resumen : 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. Mención de responsabilidad : María E Teresa-Rodrigo, Juliane Eckhold, Beatriz Puisac, Andreas Dalski, María C Gil-Rodríguez, Diana Braunholz, Carolina Baquero, María Hernández-Marcos, Juan C de Karam, Milagros Ciero, Fernando Santos-Simarro, Pablo Lapunzina, Jolanta Wierzba, César H Casale, Feliciano J Ramos, Gabriele Gillessen-Kaesbach, Frank J Kaiser, Juan Pié Referencia : Int J Mol Sci. 2014 Jun 10;15(6):10350-64. DOI (Digital Object Identifier) : 10.3390/ijms150610350 PMID : 24918291 Derechos de uso : CC BY En línea : https://www.mdpi.com/1422-0067/15/6/10350 Enlace permanente : https://hospitalpablotobon.cloudbiteca.com/pmb/opac_css/index.php?lvl=notice_display&id=3782

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