De novo Heterozygous Mutations in SMC3 Cause a Range of Cornelia De Lange Syndrome-Overlapping Phenotypes
- Autores
- Gil Rodríguez, María Concepción; Deardorff, Matthew A.; Ansari, Morad; Tan, Christopher A.; Parenti, Ilaria; Baquero Montoya, Carolina; Ousager, Liliana B.; Puisac, Beatriz; Hernández Marcos, María; Teresa Rodrigo, María Esperanza; Marcos Alcalde, Iñigo; Wesselink, Jan-Jaap; Lusa Bernal, Silvia; Bijlsma, Emilia K.; Braunholz, Diana; Bueno Martínez, Inés; Clark, Dina; Cooper, Nicola S.; Curry, Cynthia J.; Fisher, Richard; Fryer, Alan; Ganesh, Jaya; Gervasini, Cristina; Gillessen Kaesbach, Gabrielle; Guo, Yiran; Hakonarson, Hakon; Hopkin, Robert J.; Kaur, Maninder; Keating, Brendan J.; Kibaek, María; Kinning, Esther; Kleefstra, Tjitske; Kline, Antonie D.; Kuchinskaya, Ekaterina; Larizza, Lidia; Li, Yun R.; Liu, Xuanzhu; Mariani, Milena; Picker, Jonathan D.; Pié, Ángeles; Pozojevic, Jelena; Queralt, Ethel; Richer, Julie; Roeder, Elizabeth; Sinha, Anubha; Scott, Richard H.; So, Joyce; Wusik, Katherine A.; Wilson, Louise; Zhang, Jianguo; Gómez Puertas, Paulino; Casale, Cesar Horacio; Ström, Lena; Selicorni, Angelo; Ramos, Feliciano J.; Jackson. Laird G.; Krantz, Ian D.; Das, Soma; Hennekam, Raoul C.M.; Kaiser, Frank J.; FitzPatrick, David R.; Pié, Juan
- Año de publicación
- 2015
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- 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 sixteen patients with CdLS-like features caused by mutations in SMC3. Modelling of the mutation effects on protein structure suggests a dominant-negative effect on the multimeric cohesin complex. When compared to 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.
Fil: Gil Rodríguez, María Concepción. Universidad de Zaragoza; España
Fil: Deardorff, Matthew A.. Children´s Hospital of Philadelphia; Estados Unidos. University of Pennsylvania ; Estados Unidos
Fil: Ansari, Morad. University of Edinburgh; Reino Unido
Fil: Tan, Christopher A.. University of Chicago; Estados Unidos
Fil: Parenti, Ilaria. Universität zu Lübeck; Alemania. Università degli Studi di Milano; Italia
Fil: Baquero Montoya, Carolina. Universidad de Zaragoza; España. Hospital Pablo Tobón Uribe; Colombia
Fil: Ousager, Liliana B.. Odense University Hospital; Dinamarca
Fil: Puisac, Beatriz. Universidad de Zaragoza; España
Fil: Hernández Marcos, María. Universidad de Zaragoza; España
Fil: Teresa Rodrigo, María Esperanza. Universidad de Zaragoza; España
Fil: Marcos Alcalde, Iñigo. Centro de Biología Molecular ; España
Fil: Wesselink, Jan-Jaap. Biomol‐Informatics SL; España
Fil: Lusa Bernal, Silvia. Biomol‐Informatics SL; España
Fil: Bijlsma, Emilia K.. Leiden University; Países Bajos
Fil: Braunholz, Diana. Universität zu Lübeck; Alemania
Fil: Bueno Martínez, Inés. Universidad de Zaragoza; España. Hospital Clínico Universitario ; España
Fil: Clark, Dina. Children´s Hospital of Philadelphia; Estados Unidos
Fil: Cooper, Nicola S.. Birmingham Women´s Hospital; Reino Unido
Fil: Curry, Cynthia J.. University of California; Estados Unidos
Fil: Fisher, Richard. The James Cook University Hospital; Reino Unido
Fil: Fryer, Alan. Liverpool Women´s Hospital and Alder Hey Children´s Hospital; Reino Unido
Fil: Ganesh, Jaya. University of Pennsylvania ; Estados Unidos. Children´s Hospital of Philadelphia; Estados Unidos
Fil: Gervasini, Cristina. Università degli Studi di Milano; Italia
Fil: Gillessen Kaesbach, Gabrielle. Universität zu Lübeck; Alemania
Fil: Guo, Yiran. Children´s Hospital of Philadelphia; Estados Unidos
Fil: Hakonarson, Hakon. University of Pennsylvania ; Estados Unidos. Children´s Hospital of Philadelphia; Estados Unidos
Fil: Hopkin, Robert J.. Cincinnati Children´s Hospital Medical Center; Estados Unidos
Fil: Kaur, Maninder. University of Pennsylvania ; Estados Unidos. Children´s Hospital of Philadelphia; Estados Unidos
Fil: Keating, Brendan J.. University of Pennsylvania ; Estados Unidos. Children´s Hospital of Philadelphia; Estados Unidos
Fil: Kibaek, María. HC Andersen Children´s Hospital; Dinamarca
Fil: Kinning, Esther. Southern General Hospital; Reino Unido
Fil: Kleefstra, Tjitske. Radboud Universiteit Nijmegen; Países Bajos
Fil: Kline, Antonie D.. Greater Baltimore Medical Center; Estados Unidos
Fil: Kuchinskaya, Ekaterina. Linköping University Hospital; Suecia
Fil: Larizza, Lidia. Università degli Studi di Milano; Italia
Fil: Li, Yun R.. University of Pennsylvania ; Estados Unidos. Children´s Hospital of Philadelphia; Estados Unidos
Fil: Liu, Xuanzhu. BGI-Shenzhen; China
Fil: Mariani, Milena. Fobdazione MBBM AOS Gerardo; Italia
Fil: Picker, Jonathan D.. Boston Children´s Hospital; Estados Unidos
Fil: Pié, Ángeles. Universidad de Zaragoza; España
Fil: Pozojevic, Jelena. Universität zu Lübeck; Alemania
Fil: Queralt, Ethel. L´Hospitalet de Llobregat; España
Fil: Richer, Julie. University of Ottawa; Canadá
Fil: Roeder, Elizabeth. University of Texas San Antonio; Estados Unidos
Fil: Sinha, Anubha. Birmingham Women´s Hospital; Reino Unido
Fil: Scott, Richard H.. Great Ormond Street Hospital; Reino Unido. UCL Intitute of Child Health; Reino Unido
Fil: So, Joyce. CAMH; Canadá
Fil: Wusik, Katherine A.. Cincinnati Children´s Hospital Medical Center; Estados Unidos
Fil: Wilson, Louise. Great Ormond Street Hospital; Reino Unido
Fil: Zhang, Jianguo. BGI-Shenzhen; China
Fil: Gómez Puertas, Paulino. Centro de Biología Molecular ; España
Fil: Casale, Cesar Horacio. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Departamento de Biología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Ström, Lena. Karolinska Institutet; Suecia
Fil: Selicorni, Angelo. Fobdazione MBBM AOS Gerardo; Italia
Fil: Ramos, Feliciano J.. Universidad de Zaragoza; España. Hospital Clínico Universitario ; España
Fil: Jackson. Laird G.. Drexel University; Estados Unidos
Fil: Krantz, Ian D.. University of Pennsylvania ; Estados Unidos. Children´s Hospital of Philadelphia; Estados Unidos
Fil: Das, Soma. University of Chicago; Estados Unidos
Fil: Hennekam, Raoul C.M.. University of Amsterdam; Países Bajos
Fil: Kaiser, Frank J.. Universität zu Lübeck; Alemania
Fil: FitzPatrick, David R.. University of Edinburgh; Reino Unido
Fil: Pié, Juan. Universidad de Zaragoza; España - Materia
-
Cornelia
Lange
Nipbl
Smc1a - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
.jpg)
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/46500
Ver los metadatos del registro completo
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De novo Heterozygous Mutations in SMC3 Cause a Range of Cornelia De Lange Syndrome-Overlapping PhenotypesGil Rodríguez, María ConcepciónDeardorff, Matthew A.Ansari, MoradTan, Christopher A.Parenti, IlariaBaquero Montoya, CarolinaOusager, Liliana B.Puisac, BeatrizHernández Marcos, MaríaTeresa Rodrigo, María EsperanzaMarcos Alcalde, IñigoWesselink, Jan-JaapLusa Bernal, SilviaBijlsma, Emilia K.Braunholz, DianaBueno Martínez, InésClark, DinaCooper, Nicola S.Curry, Cynthia J.Fisher, RichardFryer, AlanGanesh, JayaGervasini, CristinaGillessen Kaesbach, GabrielleGuo, YiranHakonarson, HakonHopkin, Robert J.Kaur, ManinderKeating, Brendan J.Kibaek, MaríaKinning, EstherKleefstra, TjitskeKline, Antonie D.Kuchinskaya, EkaterinaLarizza, LidiaLi, Yun R.Liu, XuanzhuMariani, MilenaPicker, Jonathan D.Pié, ÁngelesPozojevic, JelenaQueralt, EthelRicher, JulieRoeder, ElizabethSinha, AnubhaScott, Richard H.So, JoyceWusik, Katherine A.Wilson, LouiseZhang, JianguoGómez Puertas, PaulinoCasale, Cesar HoracioStröm, LenaSelicorni, AngeloRamos, Feliciano J.Jackson. Laird G.Krantz, Ian D.Das, SomaHennekam, Raoul C.M.Kaiser, Frank J.FitzPatrick, David R.Pié, JuanCorneliaLangeNipblSmc1ahttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Cornelia 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 sixteen patients with CdLS-like features caused by mutations in SMC3. Modelling of the mutation effects on protein structure suggests a dominant-negative effect on the multimeric cohesin complex. When compared to 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.Fil: Gil Rodríguez, María Concepción. Universidad de Zaragoza; EspañaFil: Deardorff, Matthew A.. Children´s Hospital of Philadelphia; Estados Unidos. University of Pennsylvania ; Estados UnidosFil: Ansari, Morad. University of Edinburgh; Reino UnidoFil: Tan, Christopher A.. University of Chicago; Estados UnidosFil: Parenti, Ilaria. Universität zu Lübeck; Alemania. Università degli Studi di Milano; ItaliaFil: Baquero Montoya, Carolina. Universidad de Zaragoza; España. Hospital Pablo Tobón Uribe; ColombiaFil: Ousager, Liliana B.. Odense University Hospital; DinamarcaFil: Puisac, Beatriz. Universidad de Zaragoza; EspañaFil: Hernández Marcos, María. Universidad de Zaragoza; EspañaFil: Teresa Rodrigo, María Esperanza. Universidad de Zaragoza; EspañaFil: Marcos Alcalde, Iñigo. Centro de Biología Molecular ; EspañaFil: Wesselink, Jan-Jaap. Biomol‐Informatics SL; EspañaFil: Lusa Bernal, Silvia. Biomol‐Informatics SL; EspañaFil: Bijlsma, Emilia K.. Leiden University; Países BajosFil: Braunholz, Diana. Universität zu Lübeck; AlemaniaFil: Bueno Martínez, Inés. Universidad de Zaragoza; España. Hospital Clínico Universitario ; EspañaFil: Clark, Dina. Children´s Hospital of Philadelphia; Estados UnidosFil: Cooper, Nicola S.. Birmingham Women´s Hospital; Reino UnidoFil: Curry, Cynthia J.. University of California; Estados UnidosFil: Fisher, Richard. The James Cook University Hospital; Reino UnidoFil: Fryer, Alan. Liverpool Women´s Hospital and Alder Hey Children´s Hospital; Reino UnidoFil: Ganesh, Jaya. University of Pennsylvania ; Estados Unidos. Children´s Hospital of Philadelphia; Estados UnidosFil: Gervasini, Cristina. Università degli Studi di Milano; ItaliaFil: Gillessen Kaesbach, Gabrielle. Universität zu Lübeck; AlemaniaFil: Guo, Yiran. Children´s Hospital of Philadelphia; Estados UnidosFil: Hakonarson, Hakon. University of Pennsylvania ; Estados Unidos. Children´s Hospital of Philadelphia; Estados UnidosFil: Hopkin, Robert J.. Cincinnati Children´s Hospital Medical Center; Estados UnidosFil: Kaur, Maninder. University of Pennsylvania ; Estados Unidos. Children´s Hospital of Philadelphia; Estados UnidosFil: Keating, Brendan J.. University of Pennsylvania ; Estados Unidos. Children´s Hospital of Philadelphia; Estados UnidosFil: Kibaek, María. HC Andersen Children´s Hospital; DinamarcaFil: Kinning, Esther. Southern General Hospital; Reino UnidoFil: Kleefstra, Tjitske. Radboud Universiteit Nijmegen; Países BajosFil: Kline, Antonie D.. Greater Baltimore Medical Center; Estados UnidosFil: Kuchinskaya, Ekaterina. Linköping University Hospital; SueciaFil: Larizza, Lidia. Università degli Studi di Milano; ItaliaFil: Li, Yun R.. University of Pennsylvania ; Estados Unidos. Children´s Hospital of Philadelphia; Estados UnidosFil: Liu, Xuanzhu. BGI-Shenzhen; ChinaFil: Mariani, Milena. Fobdazione MBBM AOS Gerardo; ItaliaFil: Picker, Jonathan D.. Boston Children´s Hospital; Estados UnidosFil: Pié, Ángeles. Universidad de Zaragoza; EspañaFil: Pozojevic, Jelena. Universität zu Lübeck; AlemaniaFil: Queralt, Ethel. L´Hospitalet de Llobregat; EspañaFil: Richer, Julie. University of Ottawa; CanadáFil: Roeder, Elizabeth. University of Texas San Antonio; Estados UnidosFil: Sinha, Anubha. Birmingham Women´s Hospital; Reino UnidoFil: Scott, Richard H.. Great Ormond Street Hospital; Reino Unido. UCL Intitute of Child Health; Reino UnidoFil: So, Joyce. CAMH; CanadáFil: Wusik, Katherine A.. Cincinnati Children´s Hospital Medical Center; Estados UnidosFil: Wilson, Louise. Great Ormond Street Hospital; Reino UnidoFil: Zhang, Jianguo. BGI-Shenzhen; ChinaFil: Gómez Puertas, Paulino. Centro de Biología Molecular ; EspañaFil: Casale, Cesar Horacio. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Departamento de Biología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ström, Lena. Karolinska Institutet; SueciaFil: Selicorni, Angelo. Fobdazione MBBM AOS Gerardo; ItaliaFil: Ramos, Feliciano J.. Universidad de Zaragoza; España. Hospital Clínico Universitario ; EspañaFil: Jackson. Laird G.. Drexel University; Estados UnidosFil: Krantz, Ian D.. University of Pennsylvania ; Estados Unidos. Children´s Hospital of Philadelphia; Estados UnidosFil: Das, Soma. University of Chicago; Estados UnidosFil: Hennekam, Raoul C.M.. University of Amsterdam; Países BajosFil: Kaiser, Frank J.. Universität zu Lübeck; AlemaniaFil: FitzPatrick, David R.. University of Edinburgh; Reino UnidoFil: Pié, Juan. Universidad de Zaragoza; EspañaWiley-liss, Div John Wiley & Sons Inc2015-03-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/46500Gil Rodríguez, María Concepción; Deardorff, Matthew A.; Ansari, Morad; Tan, Christopher A.; Parenti, Ilaria; et al.; De novo Heterozygous Mutations in SMC3 Cause a Range of Cornelia De Lange Syndrome-Overlapping Phenotypes; Wiley-liss, Div John Wiley & Sons Inc; Human Mutation; 36; 4; 30-2-2015; 454-4621059-77941098-1004CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1002/humu.22761info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1002/humu.22761info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:27:32Zoai:ri.conicet.gov.ar:11336/46500instacron: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:34982025-10-22 11:27:32.821CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
| dc.title.none.fl_str_mv |
De novo Heterozygous Mutations in SMC3 Cause a Range of Cornelia De Lange Syndrome-Overlapping Phenotypes |
| title |
De novo Heterozygous Mutations in SMC3 Cause a Range of Cornelia De Lange Syndrome-Overlapping Phenotypes |
| spellingShingle |
De novo Heterozygous Mutations in SMC3 Cause a Range of Cornelia De Lange Syndrome-Overlapping Phenotypes Gil Rodríguez, María Concepción Cornelia Lange Nipbl Smc1a |
| title_short |
De novo Heterozygous Mutations in SMC3 Cause a Range of Cornelia De Lange Syndrome-Overlapping Phenotypes |
| title_full |
De novo Heterozygous Mutations in SMC3 Cause a Range of Cornelia De Lange Syndrome-Overlapping Phenotypes |
| title_fullStr |
De novo Heterozygous Mutations in SMC3 Cause a Range of Cornelia De Lange Syndrome-Overlapping Phenotypes |
| title_full_unstemmed |
De novo Heterozygous Mutations in SMC3 Cause a Range of Cornelia De Lange Syndrome-Overlapping Phenotypes |
| title_sort |
De novo Heterozygous Mutations in SMC3 Cause a Range of Cornelia De Lange Syndrome-Overlapping Phenotypes |
| dc.creator.none.fl_str_mv |
Gil Rodríguez, María Concepción Deardorff, Matthew A. Ansari, Morad Tan, Christopher A. Parenti, Ilaria Baquero Montoya, Carolina Ousager, Liliana B. Puisac, Beatriz Hernández Marcos, María Teresa Rodrigo, María Esperanza Marcos Alcalde, Iñigo Wesselink, Jan-Jaap Lusa Bernal, Silvia Bijlsma, Emilia K. Braunholz, Diana Bueno Martínez, Inés Clark, Dina Cooper, Nicola S. Curry, Cynthia J. Fisher, Richard Fryer, Alan Ganesh, Jaya Gervasini, Cristina Gillessen Kaesbach, Gabrielle Guo, Yiran Hakonarson, Hakon Hopkin, Robert J. Kaur, Maninder Keating, Brendan J. Kibaek, María Kinning, Esther Kleefstra, Tjitske Kline, Antonie D. Kuchinskaya, Ekaterina Larizza, Lidia Li, Yun R. Liu, Xuanzhu Mariani, Milena Picker, Jonathan D. Pié, Ángeles Pozojevic, Jelena Queralt, Ethel Richer, Julie Roeder, Elizabeth Sinha, Anubha Scott, Richard H. So, Joyce Wusik, Katherine A. Wilson, Louise Zhang, Jianguo Gómez Puertas, Paulino Casale, Cesar Horacio Ström, Lena Selicorni, Angelo Ramos, Feliciano J. Jackson. Laird G. Krantz, Ian D. Das, Soma Hennekam, Raoul C.M. Kaiser, Frank J. FitzPatrick, David R. Pié, Juan |
| author |
Gil Rodríguez, María Concepción |
| author_facet |
Gil Rodríguez, María Concepción Deardorff, Matthew A. Ansari, Morad Tan, Christopher A. Parenti, Ilaria Baquero Montoya, Carolina Ousager, Liliana B. Puisac, Beatriz Hernández Marcos, María Teresa Rodrigo, María Esperanza Marcos Alcalde, Iñigo Wesselink, Jan-Jaap Lusa Bernal, Silvia Bijlsma, Emilia K. Braunholz, Diana Bueno Martínez, Inés Clark, Dina Cooper, Nicola S. Curry, Cynthia J. Fisher, Richard Fryer, Alan Ganesh, Jaya Gervasini, Cristina Gillessen Kaesbach, Gabrielle Guo, Yiran Hakonarson, Hakon Hopkin, Robert J. Kaur, Maninder Keating, Brendan J. Kibaek, María Kinning, Esther Kleefstra, Tjitske Kline, Antonie D. Kuchinskaya, Ekaterina Larizza, Lidia Li, Yun R. Liu, Xuanzhu Mariani, Milena Picker, Jonathan D. Pié, Ángeles Pozojevic, Jelena Queralt, Ethel Richer, Julie Roeder, Elizabeth Sinha, Anubha Scott, Richard H. So, Joyce Wusik, Katherine A. Wilson, Louise Zhang, Jianguo Gómez Puertas, Paulino Casale, Cesar Horacio Ström, Lena Selicorni, Angelo Ramos, Feliciano J. Jackson. Laird G. Krantz, Ian D. Das, Soma Hennekam, Raoul C.M. Kaiser, Frank J. FitzPatrick, David R. Pié, Juan |
| author_role |
author |
| author2 |
Deardorff, Matthew A. Ansari, Morad Tan, Christopher A. Parenti, Ilaria Baquero Montoya, Carolina Ousager, Liliana B. Puisac, Beatriz Hernández Marcos, María Teresa Rodrigo, María Esperanza Marcos Alcalde, Iñigo Wesselink, Jan-Jaap Lusa Bernal, Silvia Bijlsma, Emilia K. Braunholz, Diana Bueno Martínez, Inés Clark, Dina Cooper, Nicola S. Curry, Cynthia J. Fisher, Richard Fryer, Alan Ganesh, Jaya Gervasini, Cristina Gillessen Kaesbach, Gabrielle Guo, Yiran Hakonarson, Hakon Hopkin, Robert J. Kaur, Maninder Keating, Brendan J. Kibaek, María Kinning, Esther Kleefstra, Tjitske Kline, Antonie D. Kuchinskaya, Ekaterina Larizza, Lidia Li, Yun R. Liu, Xuanzhu Mariani, Milena Picker, Jonathan D. Pié, Ángeles Pozojevic, Jelena Queralt, Ethel Richer, Julie Roeder, Elizabeth Sinha, Anubha Scott, Richard H. So, Joyce Wusik, Katherine A. Wilson, Louise Zhang, Jianguo Gómez Puertas, Paulino Casale, Cesar Horacio Ström, Lena Selicorni, Angelo Ramos, Feliciano J. Jackson. Laird G. Krantz, Ian D. Das, Soma Hennekam, Raoul C.M. Kaiser, Frank J. FitzPatrick, David R. Pié, Juan |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
Cornelia Lange Nipbl Smc1a |
| topic |
Cornelia Lange Nipbl Smc1a |
| purl_subject.fl_str_mv |
https://purl.org/becyt/ford/3.3 https://purl.org/becyt/ford/3 |
| dc.description.none.fl_txt_mv |
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 sixteen patients with CdLS-like features caused by mutations in SMC3. Modelling of the mutation effects on protein structure suggests a dominant-negative effect on the multimeric cohesin complex. When compared to 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. Fil: Gil Rodríguez, María Concepción. Universidad de Zaragoza; España Fil: Deardorff, Matthew A.. Children´s Hospital of Philadelphia; Estados Unidos. University of Pennsylvania ; Estados Unidos Fil: Ansari, Morad. University of Edinburgh; Reino Unido Fil: Tan, Christopher A.. University of Chicago; Estados Unidos Fil: Parenti, Ilaria. Universität zu Lübeck; Alemania. Università degli Studi di Milano; Italia Fil: Baquero Montoya, Carolina. Universidad de Zaragoza; España. Hospital Pablo Tobón Uribe; Colombia Fil: Ousager, Liliana B.. Odense University Hospital; Dinamarca Fil: Puisac, Beatriz. Universidad de Zaragoza; España Fil: Hernández Marcos, María. Universidad de Zaragoza; España Fil: Teresa Rodrigo, María Esperanza. Universidad de Zaragoza; España Fil: Marcos Alcalde, Iñigo. Centro de Biología Molecular ; España Fil: Wesselink, Jan-Jaap. Biomol‐Informatics SL; España Fil: Lusa Bernal, Silvia. Biomol‐Informatics SL; España Fil: Bijlsma, Emilia K.. Leiden University; Países Bajos Fil: Braunholz, Diana. Universität zu Lübeck; Alemania Fil: Bueno Martínez, Inés. Universidad de Zaragoza; España. Hospital Clínico Universitario ; España Fil: Clark, Dina. Children´s Hospital of Philadelphia; Estados Unidos Fil: Cooper, Nicola S.. Birmingham Women´s Hospital; Reino Unido Fil: Curry, Cynthia J.. University of California; Estados Unidos Fil: Fisher, Richard. The James Cook University Hospital; Reino Unido Fil: Fryer, Alan. Liverpool Women´s Hospital and Alder Hey Children´s Hospital; Reino Unido Fil: Ganesh, Jaya. University of Pennsylvania ; Estados Unidos. Children´s Hospital of Philadelphia; Estados Unidos Fil: Gervasini, Cristina. Università degli Studi di Milano; Italia Fil: Gillessen Kaesbach, Gabrielle. Universität zu Lübeck; Alemania Fil: Guo, Yiran. Children´s Hospital of Philadelphia; Estados Unidos Fil: Hakonarson, Hakon. University of Pennsylvania ; Estados Unidos. Children´s Hospital of Philadelphia; Estados Unidos Fil: Hopkin, Robert J.. Cincinnati Children´s Hospital Medical Center; Estados Unidos Fil: Kaur, Maninder. University of Pennsylvania ; Estados Unidos. Children´s Hospital of Philadelphia; Estados Unidos Fil: Keating, Brendan J.. University of Pennsylvania ; Estados Unidos. Children´s Hospital of Philadelphia; Estados Unidos Fil: Kibaek, María. HC Andersen Children´s Hospital; Dinamarca Fil: Kinning, Esther. Southern General Hospital; Reino Unido Fil: Kleefstra, Tjitske. Radboud Universiteit Nijmegen; Países Bajos Fil: Kline, Antonie D.. Greater Baltimore Medical Center; Estados Unidos Fil: Kuchinskaya, Ekaterina. Linköping University Hospital; Suecia Fil: Larizza, Lidia. Università degli Studi di Milano; Italia Fil: Li, Yun R.. University of Pennsylvania ; Estados Unidos. Children´s Hospital of Philadelphia; Estados Unidos Fil: Liu, Xuanzhu. BGI-Shenzhen; China Fil: Mariani, Milena. Fobdazione MBBM AOS Gerardo; Italia Fil: Picker, Jonathan D.. Boston Children´s Hospital; Estados Unidos Fil: Pié, Ángeles. Universidad de Zaragoza; España Fil: Pozojevic, Jelena. Universität zu Lübeck; Alemania Fil: Queralt, Ethel. L´Hospitalet de Llobregat; España Fil: Richer, Julie. University of Ottawa; Canadá Fil: Roeder, Elizabeth. University of Texas San Antonio; Estados Unidos Fil: Sinha, Anubha. Birmingham Women´s Hospital; Reino Unido Fil: Scott, Richard H.. Great Ormond Street Hospital; Reino Unido. UCL Intitute of Child Health; Reino Unido Fil: So, Joyce. CAMH; Canadá Fil: Wusik, Katherine A.. Cincinnati Children´s Hospital Medical Center; Estados Unidos Fil: Wilson, Louise. Great Ormond Street Hospital; Reino Unido Fil: Zhang, Jianguo. BGI-Shenzhen; China Fil: Gómez Puertas, Paulino. Centro de Biología Molecular ; España Fil: Casale, Cesar Horacio. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Departamento de Biología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Ström, Lena. Karolinska Institutet; Suecia Fil: Selicorni, Angelo. Fobdazione MBBM AOS Gerardo; Italia Fil: Ramos, Feliciano J.. Universidad de Zaragoza; España. Hospital Clínico Universitario ; España Fil: Jackson. Laird G.. Drexel University; Estados Unidos Fil: Krantz, Ian D.. University of Pennsylvania ; Estados Unidos. Children´s Hospital of Philadelphia; Estados Unidos Fil: Das, Soma. University of Chicago; Estados Unidos Fil: Hennekam, Raoul C.M.. University of Amsterdam; Países Bajos Fil: Kaiser, Frank J.. Universität zu Lübeck; Alemania Fil: FitzPatrick, David R.. University of Edinburgh; Reino Unido Fil: Pié, Juan. Universidad de Zaragoza; España |
| description |
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 sixteen patients with CdLS-like features caused by mutations in SMC3. Modelling of the mutation effects on protein structure suggests a dominant-negative effect on the multimeric cohesin complex. When compared to 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. |
| publishDate |
2015 |
| dc.date.none.fl_str_mv |
2015-03-02 |
| 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/11336/46500 Gil Rodríguez, María Concepción; Deardorff, Matthew A.; Ansari, Morad; Tan, Christopher A.; Parenti, Ilaria; et al.; De novo Heterozygous Mutations in SMC3 Cause a Range of Cornelia De Lange Syndrome-Overlapping Phenotypes; Wiley-liss, Div John Wiley & Sons Inc; Human Mutation; 36; 4; 30-2-2015; 454-462 1059-7794 1098-1004 CONICET Digital CONICET |
| url |
http://hdl.handle.net/11336/46500 |
| identifier_str_mv |
Gil Rodríguez, María Concepción; Deardorff, Matthew A.; Ansari, Morad; Tan, Christopher A.; Parenti, Ilaria; et al.; De novo Heterozygous Mutations in SMC3 Cause a Range of Cornelia De Lange Syndrome-Overlapping Phenotypes; Wiley-liss, Div John Wiley & Sons Inc; Human Mutation; 36; 4; 30-2-2015; 454-462 1059-7794 1098-1004 CONICET Digital CONICET |
| dc.language.none.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/doi/10.1002/humu.22761 info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1002/humu.22761 |
| 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 |
Wiley-liss, Div John Wiley & Sons Inc |
| publisher.none.fl_str_mv |
Wiley-liss, Div John Wiley & Sons Inc |
| 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 |
| _version_ |
1846781844850212864 |
| score |
12.982451 |