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Autor Carolina Baquero Montoya
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Médica Pediatra Especialista en Genética Clínica y Metabolismo, Hospital Pablo Tobón Uribe
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Título : ANKRD11 variants: KBG syndrome and beyond Tipo de documento : documento electrónico Autores : Carolina Baquero Montoya, Fecha de publicación : 2021 Títulos uniformes : Clinical Genetics Idioma : Inglés (eng) Palabras clave : ANKRD11 Cornelia de Lange syndrome (CdLS) KBG syndrome (KBGS) chromatinopathies developmental disorders Resumen : Mutations affecting the transcriptional regulator Ankyrin Repeat Domain 11 (ANKRD11) are mainly associated with the multisystem developmental disorder known as KBG syndrome, but have also been identified in individuals with Cornelia de Lange syndrome (CdLS) and other developmental disorders caused by variants affecting different chromatin regulators. The extensive functional overlap of these proteins results in shared phenotypical features, which complicate the assessment of the clinical diagnosis. Additionally, re-evaluation of individuals at a later age occasionally reveals that the initial phenotype has evolved toward clinical features more reminiscent of a developmental disorder different from the one that was initially diagnosed. For this reason, variants in ANKRD11 can be ascribed to a broader class of disorders that fall within the category of the so-called chromatinopathies. In this work, we report on the clinical characterization of 23 individuals with variants in ANKRD11. The subjects present primarily with developmental delay, intellectual disability and dysmorphic features, and all but two received an initial clinical diagnosis of either KBG syndrome or CdLS. The number and the severity of the clinical signs are overlapping but variable and result in a broad spectrum of phenotypes, which could be partially accounted for by the presence of additional molecular diagnoses and distinct pathogenic mechanisms. Mención de responsabilidad : Ilaria Parenti, Mark B. Mallozzi, Irina Hüning, Cristina Gervasini, Alma Kuechler, Emanuele Agolini, Beate Albrecht, Carolina Baquero-Montoya, Axel Bohring, Nuria C. Bramswig, Andreas Busche, Andreas Dalski, Yiran Guo, Britta Hanker, Yorck Hellenbroich, Denise Horn, A. Micheil Innes, Chiara Leoni, Yun R. Li, Sally Ann Lynch, Milena Mariani, Livija Medne, Barbara Mikat, Donatella Milani, Roberta Onesimo, Xilma Ortiz-Gonzalez, Eva Christina Prott, Heiko Reutter, Eva Rossier, Angelo Selicorni, Peter Wieacker, Alisha Wilkens, Dagmar Wieczorek, Elaine H. Zackai, Giuseppe Zampino, Birgit Zirn, Hakon Hakonarson, Matthew A. Deardorff, Gabriele Gillessen-Kaesbach, Frank J. Kaiser Referencia : Clin Genet. 2021 Aug;100(2):187-200 DOI (Digital Object Identifier) : 10.1111/cge.13977 PMID : 33955014 Derechos de uso : CC BY En línea : https://onlinelibrary.wiley.com/doi/10.1111/cge.13977 Enlace permanente : https://hospitalpablotobon.cloudbiteca.com/pmb/opac_css/index.php?lvl=notice_display&id=5806 ANKRD11 variants: KBG syndrome and beyond [documento electrónico] / Carolina Baquero Montoya, . - 2021.
Obra : Clinical Genetics
Idioma : Inglés (eng)
Palabras clave : ANKRD11 Cornelia de Lange syndrome (CdLS) KBG syndrome (KBGS) chromatinopathies developmental disorders Resumen : Mutations affecting the transcriptional regulator Ankyrin Repeat Domain 11 (ANKRD11) are mainly associated with the multisystem developmental disorder known as KBG syndrome, but have also been identified in individuals with Cornelia de Lange syndrome (CdLS) and other developmental disorders caused by variants affecting different chromatin regulators. The extensive functional overlap of these proteins results in shared phenotypical features, which complicate the assessment of the clinical diagnosis. Additionally, re-evaluation of individuals at a later age occasionally reveals that the initial phenotype has evolved toward clinical features more reminiscent of a developmental disorder different from the one that was initially diagnosed. For this reason, variants in ANKRD11 can be ascribed to a broader class of disorders that fall within the category of the so-called chromatinopathies. In this work, we report on the clinical characterization of 23 individuals with variants in ANKRD11. The subjects present primarily with developmental delay, intellectual disability and dysmorphic features, and all but two received an initial clinical diagnosis of either KBG syndrome or CdLS. The number and the severity of the clinical signs are overlapping but variable and result in a broad spectrum of phenotypes, which could be partially accounted for by the presence of additional molecular diagnoses and distinct pathogenic mechanisms. Mención de responsabilidad : Ilaria Parenti, Mark B. Mallozzi, Irina Hüning, Cristina Gervasini, Alma Kuechler, Emanuele Agolini, Beate Albrecht, Carolina Baquero-Montoya, Axel Bohring, Nuria C. Bramswig, Andreas Busche, Andreas Dalski, Yiran Guo, Britta Hanker, Yorck Hellenbroich, Denise Horn, A. Micheil Innes, Chiara Leoni, Yun R. Li, Sally Ann Lynch, Milena Mariani, Livija Medne, Barbara Mikat, Donatella Milani, Roberta Onesimo, Xilma Ortiz-Gonzalez, Eva Christina Prott, Heiko Reutter, Eva Rossier, Angelo Selicorni, Peter Wieacker, Alisha Wilkens, Dagmar Wieczorek, Elaine H. Zackai, Giuseppe Zampino, Birgit Zirn, Hakon Hakonarson, Matthew A. Deardorff, Gabriele Gillessen-Kaesbach, Frank J. Kaiser Referencia : Clin Genet. 2021 Aug;100(2):187-200 DOI (Digital Object Identifier) : 10.1111/cge.13977 PMID : 33955014 Derechos de uso : CC BY En línea : https://onlinelibrary.wiley.com/doi/10.1111/cge.13977 Enlace permanente : https://hospitalpablotobon.cloudbiteca.com/pmb/opac_css/index.php?lvl=notice_display&id=5806 Reserva
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2021-056Adobe Acrobat PDFEnfermedad por almacenamiento de glucógeno de tipo III en pacientes colombianos: caracterización clínica y molecular / Carolina Baquero Montoya ; María Elsy Sepúlveda Hincapie
Título : Enfermedad por almacenamiento de glucógeno de tipo III en pacientes colombianos: caracterización clínica y molecular Otros títulos : Molecular and clinical characterization of Colombian patients suffering from type III glycogen storage disease Tipo de documento : documento electrónico Autores : Carolina Baquero Montoya, ; María Elsy Sepúlveda Hincapie, Fecha de publicación : 2018 Títulos uniformes : Biomédica Idioma : Español (spa) Palabras clave : Enfermedad del almacenamiento de glucógeno de tipo III/diagnóstico glucógeno sistema de la enzima desramificadora del glucógeno glucogenólisis Resumen : Introducción: La enfermedad por almacenamiento de glucógeno de tipo III es una alteración autosómica recesiva, en la cual las mutaciones del gen AGL causan una deficiencia en la enzima desramificadora de glucógeno. Se caracteriza por hipoglucemia, hepatomegalia y miopatías progresivas. El análisis molecular del gen AGL ha evidenciado mutaciones que difieren según la población estudiada. En la actualidad, no existen reportes que describan mutaciones en el AGL de pacientes colombianos con esta condición. Objetivo: Describir las características clínicas y moleculares de diez pacientes colombianos con enfermedad por almacenamiento del glucógeno de tipo III. Materiales y métodos: Se analizaron diez pacientes pediátricos colombianos con la enfermedad y se hizo su estudio genético mediante la secuenciación de las regiones que codifican y las intrónicas circundantes del gen AGL con el método de Sanger. Resultados: Todos los pacientes tenían el fenotipo clásico de la enfermedad. El estudio genético reveló la mutación p.Arg910X en dos pacientes. Uno presentó la mutación p.Glu1072AspfsX36 y otro resultó heterocigoto compuesto con las mutaciones p.Arg910X y p.Glu1072AspfsX36. Asimismo, en tres pacientes se detectó la deleción de los exones 4, 5 y 6 del gen AGL. Los estudios de simulación computacional predijeron que estos defectos eran patogénicos. En tres pacientes no se encontraron mutaciones en las regiones amplificadas. Conclusión: Se encontraron mutaciones y deleciones que explican el fenotipo clínico de los pacientes. Este es el primer reporte en el que se describe el fenotipo clínico y el espectro de mutaciones en el gen AGL de pacientes colombianos, lo cual es importante para ofrecer un apropiado pronóstico, y asesoría genética al paciente y a su familia. Mención de responsabilidad : Carolina Mantilla, Mónica Toro, María Elsy Sepúlveda, Margarita Insuasty, Diana Di Filippo, Juan Álvaro López, Carolina Baquero, María Cristina Navas, Andrés Augusto Arias Referencia : Biomedica. 2018 May 1;38(0):30-42. DOI (Digital Object Identifier) : 10.7705/biomedica.v38i0.3454 PMID : 29809327 En línea : https://www.revistabiomedica.org/index.php/biomedica/article/view/3454 Enlace permanente : https://hospitalpablotobon.cloudbiteca.com/pmb/opac_css/index.php?lvl=notice_display&id=4119 Enfermedad por almacenamiento de glucógeno de tipo III en pacientes colombianos: caracterización clínica y molecular = Molecular and clinical characterization of Colombian patients suffering from type III glycogen storage disease [documento electrónico] / Carolina Baquero Montoya, ; María Elsy Sepúlveda Hincapie, . - 2018.
Obra : Biomédica
Idioma : Español (spa)
Palabras clave : Enfermedad del almacenamiento de glucógeno de tipo III/diagnóstico glucógeno sistema de la enzima desramificadora del glucógeno glucogenólisis Resumen : Introducción: La enfermedad por almacenamiento de glucógeno de tipo III es una alteración autosómica recesiva, en la cual las mutaciones del gen AGL causan una deficiencia en la enzima desramificadora de glucógeno. Se caracteriza por hipoglucemia, hepatomegalia y miopatías progresivas. El análisis molecular del gen AGL ha evidenciado mutaciones que difieren según la población estudiada. En la actualidad, no existen reportes que describan mutaciones en el AGL de pacientes colombianos con esta condición. Objetivo: Describir las características clínicas y moleculares de diez pacientes colombianos con enfermedad por almacenamiento del glucógeno de tipo III. Materiales y métodos: Se analizaron diez pacientes pediátricos colombianos con la enfermedad y se hizo su estudio genético mediante la secuenciación de las regiones que codifican y las intrónicas circundantes del gen AGL con el método de Sanger. Resultados: Todos los pacientes tenían el fenotipo clásico de la enfermedad. El estudio genético reveló la mutación p.Arg910X en dos pacientes. Uno presentó la mutación p.Glu1072AspfsX36 y otro resultó heterocigoto compuesto con las mutaciones p.Arg910X y p.Glu1072AspfsX36. Asimismo, en tres pacientes se detectó la deleción de los exones 4, 5 y 6 del gen AGL. Los estudios de simulación computacional predijeron que estos defectos eran patogénicos. En tres pacientes no se encontraron mutaciones en las regiones amplificadas. Conclusión: Se encontraron mutaciones y deleciones que explican el fenotipo clínico de los pacientes. Este es el primer reporte en el que se describe el fenotipo clínico y el espectro de mutaciones en el gen AGL de pacientes colombianos, lo cual es importante para ofrecer un apropiado pronóstico, y asesoría genética al paciente y a su familia. Mención de responsabilidad : Carolina Mantilla, Mónica Toro, María Elsy Sepúlveda, Margarita Insuasty, Diana Di Filippo, Juan Álvaro López, Carolina Baquero, María Cristina Navas, Andrés Augusto Arias Referencia : Biomedica. 2018 May 1;38(0):30-42. DOI (Digital Object Identifier) : 10.7705/biomedica.v38i0.3454 PMID : 29809327 En línea : https://www.revistabiomedica.org/index.php/biomedica/article/view/3454 Enlace permanente : https://hospitalpablotobon.cloudbiteca.com/pmb/opac_css/index.php?lvl=notice_display&id=4119 Reserva
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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 : 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 Reserva
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Título : Mutations in chromatin regulators functionally link Cornelia de Lange syndrome and clinically overlapping phenotypes Tipo de documento : documento electrónico Autores : Carolina Baquero Montoya, Fecha de publicación : 2017 Títulos uniformes : Human Genetics Idioma : Inglés (eng) Palabras clave : Intellectual Disability Sister Chromatid Cohesion Cohesin Complex Missense Substitution Depressed Nasal Bridge Resumen : The coordinated tissue-specific regulation of gene expression is essential for the proper development of all organisms. Mutations in multiple transcriptional regulators cause a group of neurodevelopmental disorders termed "transcriptomopathies" that share core phenotypical features including growth retardation, developmental delay, intellectual disability and facial dysmorphism. Cornelia de Lange syndrome (CdLS) belongs to this class of disorders and is caused by mutations in different subunits or regulators of the cohesin complex. Herein, we report on the clinical and molecular characterization of seven patients with features overlapping with CdLS who were found to carry mutations in chromatin regulators previously associated to other neurodevelopmental disorders that are frequently considered in the differential diagnosis of CdLS. The identified mutations affect the methyltransferase-encoding genes KMT2A and SETD5 and different subunits of the SWI/SNF chromatin-remodeling complex. Complementary to this, a patient with Coffin-Siris syndrome was found to carry a missense substitution in NIPBL. Our findings indicate that mutations in a variety of chromatin-associated factors result in overlapping clinical phenotypes, underscoring the genetic heterogeneity that should be considered when assessing the clinical and molecular diagnosis of neurodevelopmental syndromes. It is clear that emerging molecular mechanisms of chromatin dysregulation are central to understanding the pathogenesis of these clinically overlapping genetic disorders. Mención de responsabilidad : Ilaria Parenti, María E Teresa-Rodrigo, Jelena Pozojevic, Sara Ruiz Gil, Ingrid Bader, Diana Braunholz, Nuria C Bramswig, Cristina Gervasini, Lidia Larizza, Lutz Pfeiffer, Ferda Ozkinay, Feliciano Ramos, Benedikt Reiz, Olaf Rittinger, Tim M Strom, Erwan Watrin, Kerstin Wendt, Dagmar Wieczorek, Bernd Wollnik, Carolina Baquero-Montoya, Juan Pié, Matthew A Deardorff, Gabriele Gillessen-Kaesbach, Frank J Kaiser Referencia : Hum Genet. 2017 Mar;136(3):307-320. DOI (Digital Object Identifier) : 10.1007/s00439-017-1758-y PMID : 28120103 En línea : https://link.springer.com/article/10.1007%2Fs00439-017-1758-y Enlace permanente : https://hospitalpablotobon.cloudbiteca.com/pmb/opac_css/index.php?lvl=notice_display&id=4022 Mutations in chromatin regulators functionally link Cornelia de Lange syndrome and clinically overlapping phenotypes [documento electrónico] / Carolina Baquero Montoya, . - 2017.
Obra : Human Genetics
Idioma : Inglés (eng)
Palabras clave : Intellectual Disability Sister Chromatid Cohesion Cohesin Complex Missense Substitution Depressed Nasal Bridge Resumen : The coordinated tissue-specific regulation of gene expression is essential for the proper development of all organisms. Mutations in multiple transcriptional regulators cause a group of neurodevelopmental disorders termed "transcriptomopathies" that share core phenotypical features including growth retardation, developmental delay, intellectual disability and facial dysmorphism. Cornelia de Lange syndrome (CdLS) belongs to this class of disorders and is caused by mutations in different subunits or regulators of the cohesin complex. Herein, we report on the clinical and molecular characterization of seven patients with features overlapping with CdLS who were found to carry mutations in chromatin regulators previously associated to other neurodevelopmental disorders that are frequently considered in the differential diagnosis of CdLS. The identified mutations affect the methyltransferase-encoding genes KMT2A and SETD5 and different subunits of the SWI/SNF chromatin-remodeling complex. Complementary to this, a patient with Coffin-Siris syndrome was found to carry a missense substitution in NIPBL. Our findings indicate that mutations in a variety of chromatin-associated factors result in overlapping clinical phenotypes, underscoring the genetic heterogeneity that should be considered when assessing the clinical and molecular diagnosis of neurodevelopmental syndromes. It is clear that emerging molecular mechanisms of chromatin dysregulation are central to understanding the pathogenesis of these clinically overlapping genetic disorders. Mención de responsabilidad : Ilaria Parenti, María E Teresa-Rodrigo, Jelena Pozojevic, Sara Ruiz Gil, Ingrid Bader, Diana Braunholz, Nuria C Bramswig, Cristina Gervasini, Lidia Larizza, Lutz Pfeiffer, Ferda Ozkinay, Feliciano Ramos, Benedikt Reiz, Olaf Rittinger, Tim M Strom, Erwan Watrin, Kerstin Wendt, Dagmar Wieczorek, Bernd Wollnik, Carolina Baquero-Montoya, Juan Pié, Matthew A Deardorff, Gabriele Gillessen-Kaesbach, Frank J Kaiser Referencia : Hum Genet. 2017 Mar;136(3):307-320. DOI (Digital Object Identifier) : 10.1007/s00439-017-1758-y PMID : 28120103 En línea : https://link.springer.com/article/10.1007%2Fs00439-017-1758-y Enlace permanente : https://hospitalpablotobon.cloudbiteca.com/pmb/opac_css/index.php?lvl=notice_display&id=4022 Reserva
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Título : Identification and Functional Characterization of Two Intronic NIPBL Mutations in Two Patients with Cornelia de Lange Syndrome Tipo de documento : documento electrónico Autores : Carolina Baquero Montoya, Fecha de publicación : 2016 Títulos uniformes : Biomed Research International Idioma : Inglés (eng) Resumen : Cornelia de Lange syndrome (CdLS) is a rare genetically heterogeneous disorder with a high phenotypic variability including mental retardation, developmental delay, and limb malformations. The genetic causes in about 30% of patients with CdLS are still unknown. We report on the functional characterization of two intronic NIPBL mutations in two patients with CdLS that do not affect a conserved splice-donor or acceptor site. Interestingly, mRNA analyses showed aberrantly spliced transcripts missing exon 28 or 37, suggesting the loss of the branch site by the c.5329-15A>G transition and a disruption of the polypyrimidine by the c.6344del(-13)_(-8) deletion. While the loss of exon 28 retains the reading frame of the NIBPL transcript resulting in a shortened protein, the loss of exon 37 shifts the reading frame with the consequence of a premature stop of translation. Subsequent quantitative PCR analysis demonstrated a 30% decrease of the total NIPBL mRNA levels associated with the frameshift transcript. Consistent with our results, this patient shows a more severe phenotype compared to the patient with the aberrant transcript that retains its reading frame. Thus, intronic variants identified by sequencing analysis in CdLS diagnostics should carefully be examined before excluding them as nonrelevant to disease. Mención de responsabilidad : María E Teresa-Rodrigo, Juliane Eckhold, Beatriz Puisac, Jelena Pozojevic, Ilaria Parenti, Carolina Baquero-Montoya, María C Gil-Rodríguez, Diana Braunholz, Andreas Dalski, María Hernández-Marcos, Ariadna Ayerza, María L Bernal, Feliciano J Ramos, Dagmar Wieczorek, Gabriele Gillessen-Kaesbach, Juan Pié, Frank J Kaiser Referencia : Biomed Res Int. 2016;2016:8742939. DOI (Digital Object Identifier) : 10.1155/2016/8742939 PMID : 26925417 En línea : https://www.hindawi.com/journals/bmri/2016/8742939/ Enlace permanente : https://hospitalpablotobon.cloudbiteca.com/pmb/opac_css/index.php?lvl=notice_display&id=3985 Identification and Functional Characterization of Two Intronic NIPBL Mutations in Two Patients with Cornelia de Lange Syndrome [documento electrónico] / Carolina Baquero Montoya, . - 2016.
Obra : Biomed Research International
Idioma : Inglés (eng)
Resumen : Cornelia de Lange syndrome (CdLS) is a rare genetically heterogeneous disorder with a high phenotypic variability including mental retardation, developmental delay, and limb malformations. The genetic causes in about 30% of patients with CdLS are still unknown. We report on the functional characterization of two intronic NIPBL mutations in two patients with CdLS that do not affect a conserved splice-donor or acceptor site. Interestingly, mRNA analyses showed aberrantly spliced transcripts missing exon 28 or 37, suggesting the loss of the branch site by the c.5329-15A>G transition and a disruption of the polypyrimidine by the c.6344del(-13)_(-8) deletion. While the loss of exon 28 retains the reading frame of the NIBPL transcript resulting in a shortened protein, the loss of exon 37 shifts the reading frame with the consequence of a premature stop of translation. Subsequent quantitative PCR analysis demonstrated a 30% decrease of the total NIPBL mRNA levels associated with the frameshift transcript. Consistent with our results, this patient shows a more severe phenotype compared to the patient with the aberrant transcript that retains its reading frame. Thus, intronic variants identified by sequencing analysis in CdLS diagnostics should carefully be examined before excluding them as nonrelevant to disease. Mención de responsabilidad : María E Teresa-Rodrigo, Juliane Eckhold, Beatriz Puisac, Jelena Pozojevic, Ilaria Parenti, Carolina Baquero-Montoya, María C Gil-Rodríguez, Diana Braunholz, Andreas Dalski, María Hernández-Marcos, Ariadna Ayerza, María L Bernal, Feliciano J Ramos, Dagmar Wieczorek, Gabriele Gillessen-Kaesbach, Juan Pié, Frank J Kaiser Referencia : Biomed Res Int. 2016;2016:8742939. DOI (Digital Object Identifier) : 10.1155/2016/8742939 PMID : 26925417 En línea : https://www.hindawi.com/journals/bmri/2016/8742939/ Enlace permanente : https://hospitalpablotobon.cloudbiteca.com/pmb/opac_css/index.php?lvl=notice_display&id=3985 Reserva
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