2 búsqueda de la palabra clave 'cohesin complex'

Mutations in chromatin regulators functionally link Cornelia de Lange syndrome and clinically overlapping phenotypes / Carolina Baquero Montoya  

Público ISBD 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

Reservar este documento

Ejemplares(1)

Código de barras	Número de Ubicación	Tipo de medio	Ubicación	Sección	Estado
DD000617	AC-2017-006	Archivo digital	Producción Científica	Artículos científicos	Disponible

De novo heterozygous mutations in SMC3 cause a range of Cornelia de Lange syndrome-overlapping phenotypes / Carolina Baquero Montoya  

Público ISBD Título : De novo heterozygous mutations in SMC3 cause a range of Cornelia de Lange syndrome-overlapping phenotypes Tipo de documento : documento electrónico Autores : Carolina Baquero Montoya, Fecha de publicación : 2015 Títulos uniformes : Human Mutation Idioma : Inglés (eng) Palabras clave : Cornelia de Lange syndrome  CdLS  SMC3  cohesin complex  CdLS-overlapping phenotypes  CdLS- like Resumen : Cornelia de Lange syndrome (CdLS) is characterized by facial dysmorphism, growth failure, intellectual disability, limb malformations, and multiple organ involvement. Mutations in five genes, encoding subunits of the cohesin complex (SMC1A, SMC3, RAD21) and its regulators (NIPBL, HDAC8), account for at least 70% of patients with CdLS or CdLS‐like phenotypes. To date, only the clinical features from a single CdLS patient with SMC3 mutation has been published. Here, we report the efforts of an international research and clinical collaboration to provide clinical comparison of 16 patients with CdLS‐like features caused by mutations in SMC3. Modeling of the mutation effects on protein structure suggests a dominant‐negative effect on the multimeric cohesin complex. When compared with typical CdLS, many SMC3‐associated phenotypes are also characterized by postnatal microcephaly but with a less distinctive craniofacial appearance, a milder prenatal growth retardation that worsens in childhood, few congenital heart defects, and an absence of limb deficiencies. While most mutations are unique, two unrelated affected individuals shared the same mutation but presented with different phenotypes. This work confirms that de novo SMC3 mutations account for ∼1%–2% of CdLS‐like phenotypes. Mención de responsabilidad : María Concepción Gil-Rodríguez, Matthew A Deardorff, Morad Ansari, Christopher A Tan, Ilaria Parenti, Carolina Baquero-Montoya, Lilian B Ousager, Beatriz Puisac, María Hernández-Marcos, María Esperanza Teresa-Rodrigo, Iñigo Marcos-Alcalde, Jan-Jaap Wesselink, Silvia Lusa-Bernal, Emilia K Bijlsma, Diana Braunholz, Inés Bueno-Martinez, Dinah Clark, Nicola S Cooper, Cynthia J Curry, Richard Fisher, Alan Fryer, Jaya Ganesh, Cristina Gervasini, Gabriele Gillessen-Kaesbach, Yiran Guo, Hakon Hakonarson, Robert J Hopkin, Maninder Kaur, Brendan J Keating, María Kibaek, Esther Kinning, Tjitske Kleefstra, Antonie D Kline, Ekaterina Kuchinskaya, Lidia Larizza, Yun R Li, Xuanzhu Liu, Milena Mariani, Jonathan D Picker, Ángeles Pié, Jelena Pozojevic, Ethel Queralt, Julie Richer, Elizabeth Roeder, Anubha Sinha, Richard H Scott, Joyce So, Katherine A Wusik, Louise Wilson, Jianguo Zhang, Paulino Gómez-Puertas, César H Casale, Lena Ström, Angelo Selicorni, Feliciano J Ramos, Laird G Jackson, Ian D Krantz Referencia : Hum Mutat. 2015 Apr;36(4):454-62. DOI (Digital Object Identifier) : 10.1002/humu.22761 PMID : 25655089 En línea : https://onlinelibrary.wiley.com/doi/abs/10.1002/humu.22761 Enlace permanente : https://hospitalpablotobon.cloudbiteca.com/pmb/opac_css/index.php?lvl=notice_display&id=3922 De novo heterozygous mutations in SMC3 cause a range of Cornelia de Lange syndrome-overlapping phenotypes [documento electrónico] / Carolina Baquero Montoya,  . - 2015. Obra : Human Mutation Idioma : Inglés (eng) Palabras clave : Cornelia de Lange syndrome  CdLS  SMC3  cohesin complex  CdLS-overlapping phenotypes  CdLS- like Resumen : Cornelia de Lange syndrome (CdLS) is characterized by facial dysmorphism, growth failure, intellectual disability, limb malformations, and multiple organ involvement. Mutations in five genes, encoding subunits of the cohesin complex (SMC1A, SMC3, RAD21) and its regulators (NIPBL, HDAC8), account for at least 70% of patients with CdLS or CdLS‐like phenotypes. To date, only the clinical features from a single CdLS patient with SMC3 mutation has been published. Here, we report the efforts of an international research and clinical collaboration to provide clinical comparison of 16 patients with CdLS‐like features caused by mutations in SMC3. Modeling of the mutation effects on protein structure suggests a dominant‐negative effect on the multimeric cohesin complex. When compared with typical CdLS, many SMC3‐associated phenotypes are also characterized by postnatal microcephaly but with a less distinctive craniofacial appearance, a milder prenatal growth retardation that worsens in childhood, few congenital heart defects, and an absence of limb deficiencies. While most mutations are unique, two unrelated affected individuals shared the same mutation but presented with different phenotypes. This work confirms that de novo SMC3 mutations account for ∼1%–2% of CdLS‐like phenotypes. Mención de responsabilidad : María Concepción Gil-Rodríguez, Matthew A Deardorff, Morad Ansari, Christopher A Tan, Ilaria Parenti, Carolina Baquero-Montoya, Lilian B Ousager, Beatriz Puisac, María Hernández-Marcos, María Esperanza Teresa-Rodrigo, Iñigo Marcos-Alcalde, Jan-Jaap Wesselink, Silvia Lusa-Bernal, Emilia K Bijlsma, Diana Braunholz, Inés Bueno-Martinez, Dinah Clark, Nicola S Cooper, Cynthia J Curry, Richard Fisher, Alan Fryer, Jaya Ganesh, Cristina Gervasini, Gabriele Gillessen-Kaesbach, Yiran Guo, Hakon Hakonarson, Robert J Hopkin, Maninder Kaur, Brendan J Keating, María Kibaek, Esther Kinning, Tjitske Kleefstra, Antonie D Kline, Ekaterina Kuchinskaya, Lidia Larizza, Yun R Li, Xuanzhu Liu, Milena Mariani, Jonathan D Picker, Ángeles Pié, Jelena Pozojevic, Ethel Queralt, Julie Richer, Elizabeth Roeder, Anubha Sinha, Richard H Scott, Joyce So, Katherine A Wusik, Louise Wilson, Jianguo Zhang, Paulino Gómez-Puertas, César H Casale, Lena Ström, Angelo Selicorni, Feliciano J Ramos, Laird G Jackson, Ian D Krantz Referencia : Hum Mutat. 2015 Apr;36(4):454-62. DOI (Digital Object Identifier) : 10.1002/humu.22761 PMID : 25655089 En línea : https://onlinelibrary.wiley.com/doi/abs/10.1002/humu.22761 Enlace permanente : https://hospitalpablotobon.cloudbiteca.com/pmb/opac_css/index.php?lvl=notice_display&id=3922

Reserva

Reservar este documento

Ejemplares(1)

Código de barras	Número de Ubicación	Tipo de medio	Ubicación	Sección	Estado
DD000506	AC-2015-059	Archivo digital	Producción Científica	Artículos científicos	Disponible