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
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/46500

id CONICETDig_587c97ae6fe33c518e0c0dac4e812ffb
oai_identifier_str oai:ri.conicet.gov.ar:11336/46500
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling 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 Técnicas2025-09-29T09:58:13Zoai: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:34982025-09-29 09:58:14.239CONICET 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
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author
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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
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score 13.070432