Severe ipsilateral musculoskeletal involvement in a Cornelia de Lange patient with a novel NIPBL mutation

Autores
Baquero Montoya, Carolina; Gil Rodríguez, María Concepción; Hernández Marcos, María; Teresa Rodrigo, María Esperanza; Vicente Gabas, Alicia; Bernal, María Luisa; Casale, Cesar Horacio; Bueno Lozano, Gloria; Bueno Martínez, Inés; Queralt, Ethel; Villa, Olaya; Hernando Davalillo, Cristina; Armengol, Lluís; Gómez Puertas, Paulino; Puisac, Beatriz; Selicorni, Angelo; Ramos, Feliciano J.; Pié, Juan
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Cornelia de Lange Syndrome (CdLS) is a congenital autosomal dominant (NIPBL, SMC3 and RAD21) or X-linked (SMC1A and HDAC8) disorder characterized by facial dysmorphism, pre and postnatal growth retardation, developmental delay and/or intellectual disability, and multiorgan involvement. Musculoskeletal malformations are usually bilateral and affect mainly the upper limbs; the range goes from brachyclinodactyly to severe reduction defects. Instead lower extremities are usually less and mildly involved. Here, we report on a 3-year-old Senegalese boy with typical craniofacial CdLS features, pre and postnatal growth retardation, atrial septal defect, developmental delay and right ipsilateral limb malformations, consistent with oligodactyly of the 3rd and 4th fingers, tibial agenesis and fibula hypoplasia. Exome sequencing and Sanger sequencing showed a novel missense mutation in NIPBL gene (c.6647A>G; p.(Tyr2216Cys)), which affects a conserved residue located within NIPBL HEAT repeat elements. Pyrosequencing analysis of NIPBL gene, disclosed similar levels of wild-type and mutated alleles in DNA and RNA samples from all tissues analyzed (oral mucosa epithelial cells, peripheral blood leukocytes and fibroblasts). These findings indicated the absence of somatic mosaicism, despite of the segmental asymmetry of the limbs, and confirmed biallelic expression for NIPBL transcripts, respectively. Additionally, conditions like Split-hand/foot malformation with long-bone deficiency secondary to duplication of BHLHA9 gene have been ruled out by the array-CGH and MLPA analysis. To our knowledge, this is the first CdLS patient described with major ipsilateral malformations of both the upper and lower extremities, that even though this finding could be due to a random event, expands the spectrum of limb reduction defects in CdLS.
Fil: Baquero Montoya, Carolina. Universidad de Zaragoza; España. Hospital Pablo Tobón Uribe; Colombia
Fil: Gil Rodríguez, María Concepción. Universidad de Zaragoza; España
Fil: Hernández Marcos, María. Universidad de Zaragoza; España
Fil: Teresa Rodrigo, María Esperanza. Universidad de Zaragoza; España
Fil: Vicente Gabas, Alicia. Universidad de Zaragoza; España. Hospital Clínico Universitario “Lozano Blesa”; España
Fil: Bernal, María Luisa. Universidad de Zaragoza; España
Fil: Casale, Cesar Horacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Departamento de Biología Molecular; Argentina
Fil: Bueno Lozano, Gloria. Hospital Clínico Universitario “Lozano Blesa”; España
Fil: Bueno Martínez, Inés. Universidad de Zaragoza; España. Hospital Clínico Universitario “Lozano Blesa”; España
Fil: Queralt, Ethel. Universidad de Barcelona. Hospital Duran I Reynals. Instituto de Investigación Biomédica de Bellvitge; España
Fil: Villa, Olaya. Quantitative Genomic Medicine Laboratories; España
Fil: Hernando Davalillo, Cristina. Quantitative Genomic Medicine Laboratories; España
Fil: Armengol, Lluís. Quantitative Genomic Medicine Laboratories; España
Fil: Gómez Puertas, Paulino. Centro de Biología Molecular Severo Ochoa; España
Fil: Puisac, Beatriz. Universidad de Zaragoza; España
Fil: Selicorni, Angelo. University of Milano-Bicocca; Italia
Fil: Ramos, Feliciano J.. Universidad de Zaragoza; España. Hospital Clínico Universitario “Lozano Blesa”; España
Fil: Pié, Juan. Universidad de Zaragoza; España
Materia
BHLHA9 DUPLICATION
CDLS
CORNELIA DE LANGE SYNDROME
EXOME SEQUENCING
HEAT REPEAT
IPSILATERAL
MUSCULOSKELETAL INVOLVEMENT
NIPBL MUTATION
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/180663

id CONICETDig_ee40edc4fe1f317cb8c8bc01b56a2935
oai_identifier_str oai:ri.conicet.gov.ar:11336/180663
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Severe ipsilateral musculoskeletal involvement in a Cornelia de Lange patient with a novel NIPBL mutationBaquero Montoya, CarolinaGil Rodríguez, María ConcepciónHernández Marcos, MaríaTeresa Rodrigo, María EsperanzaVicente Gabas, AliciaBernal, María LuisaCasale, Cesar HoracioBueno Lozano, GloriaBueno Martínez, InésQueralt, EthelVilla, OlayaHernando Davalillo, CristinaArmengol, LluísGómez Puertas, PaulinoPuisac, BeatrizSelicorni, AngeloRamos, Feliciano J.Pié, JuanBHLHA9 DUPLICATIONCDLSCORNELIA DE LANGE SYNDROMEEXOME SEQUENCINGHEAT REPEATIPSILATERALMUSCULOSKELETAL INVOLVEMENTNIPBL MUTATIONhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Cornelia de Lange Syndrome (CdLS) is a congenital autosomal dominant (NIPBL, SMC3 and RAD21) or X-linked (SMC1A and HDAC8) disorder characterized by facial dysmorphism, pre and postnatal growth retardation, developmental delay and/or intellectual disability, and multiorgan involvement. Musculoskeletal malformations are usually bilateral and affect mainly the upper limbs; the range goes from brachyclinodactyly to severe reduction defects. Instead lower extremities are usually less and mildly involved. Here, we report on a 3-year-old Senegalese boy with typical craniofacial CdLS features, pre and postnatal growth retardation, atrial septal defect, developmental delay and right ipsilateral limb malformations, consistent with oligodactyly of the 3rd and 4th fingers, tibial agenesis and fibula hypoplasia. Exome sequencing and Sanger sequencing showed a novel missense mutation in NIPBL gene (c.6647A>G; p.(Tyr2216Cys)), which affects a conserved residue located within NIPBL HEAT repeat elements. Pyrosequencing analysis of NIPBL gene, disclosed similar levels of wild-type and mutated alleles in DNA and RNA samples from all tissues analyzed (oral mucosa epithelial cells, peripheral blood leukocytes and fibroblasts). These findings indicated the absence of somatic mosaicism, despite of the segmental asymmetry of the limbs, and confirmed biallelic expression for NIPBL transcripts, respectively. Additionally, conditions like Split-hand/foot malformation with long-bone deficiency secondary to duplication of BHLHA9 gene have been ruled out by the array-CGH and MLPA analysis. To our knowledge, this is the first CdLS patient described with major ipsilateral malformations of both the upper and lower extremities, that even though this finding could be due to a random event, expands the spectrum of limb reduction defects in CdLS.Fil: Baquero Montoya, Carolina. Universidad de Zaragoza; España. Hospital Pablo Tobón Uribe; ColombiaFil: Gil Rodríguez, María Concepción. Universidad de Zaragoza; EspañaFil: Hernández Marcos, María. Universidad de Zaragoza; EspañaFil: Teresa Rodrigo, María Esperanza. Universidad de Zaragoza; EspañaFil: Vicente Gabas, Alicia. Universidad de Zaragoza; España. Hospital Clínico Universitario “Lozano Blesa”; EspañaFil: Bernal, María Luisa. Universidad de Zaragoza; EspañaFil: Casale, Cesar Horacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Departamento de Biología Molecular; ArgentinaFil: Bueno Lozano, Gloria. Hospital Clínico Universitario “Lozano Blesa”; EspañaFil: Bueno Martínez, Inés. Universidad de Zaragoza; España. Hospital Clínico Universitario “Lozano Blesa”; EspañaFil: Queralt, Ethel. Universidad de Barcelona. Hospital Duran I Reynals. Instituto de Investigación Biomédica de Bellvitge; EspañaFil: Villa, Olaya. Quantitative Genomic Medicine Laboratories; EspañaFil: Hernando Davalillo, Cristina. Quantitative Genomic Medicine Laboratories; EspañaFil: Armengol, Lluís. Quantitative Genomic Medicine Laboratories; EspañaFil: Gómez Puertas, Paulino. Centro de Biología Molecular Severo Ochoa; EspañaFil: Puisac, Beatriz. Universidad de Zaragoza; EspañaFil: Selicorni, Angelo. University of Milano-Bicocca; ItaliaFil: Ramos, Feliciano J.. Universidad de Zaragoza; España. Hospital Clínico Universitario “Lozano Blesa”; EspañaFil: Pié, Juan. Universidad de Zaragoza; EspañaElsevier Science2014-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/180663Baquero Montoya, Carolina; Gil Rodríguez, María Concepción; Hernández Marcos, María; Teresa Rodrigo, María Esperanza; Vicente Gabas, Alicia; et al.; Severe ipsilateral musculoskeletal involvement in a Cornelia de Lange patient with a novel NIPBL mutation; Elsevier Science; European Journal Of Medical Genetics; 57; 9; 4-2014; 503-5091769-72121878-0849CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/ 10.1016/j.ejmg.2014.05.006info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S1769721214001189info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:59:46Zoai:ri.conicet.gov.ar:11336/180663instacron: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 09:59:46.94CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Severe ipsilateral musculoskeletal involvement in a Cornelia de Lange patient with a novel NIPBL mutation
title Severe ipsilateral musculoskeletal involvement in a Cornelia de Lange patient with a novel NIPBL mutation
spellingShingle Severe ipsilateral musculoskeletal involvement in a Cornelia de Lange patient with a novel NIPBL mutation
Baquero Montoya, Carolina
BHLHA9 DUPLICATION
CDLS
CORNELIA DE LANGE SYNDROME
EXOME SEQUENCING
HEAT REPEAT
IPSILATERAL
MUSCULOSKELETAL INVOLVEMENT
NIPBL MUTATION
title_short Severe ipsilateral musculoskeletal involvement in a Cornelia de Lange patient with a novel NIPBL mutation
title_full Severe ipsilateral musculoskeletal involvement in a Cornelia de Lange patient with a novel NIPBL mutation
title_fullStr Severe ipsilateral musculoskeletal involvement in a Cornelia de Lange patient with a novel NIPBL mutation
title_full_unstemmed Severe ipsilateral musculoskeletal involvement in a Cornelia de Lange patient with a novel NIPBL mutation
title_sort Severe ipsilateral musculoskeletal involvement in a Cornelia de Lange patient with a novel NIPBL mutation
dc.creator.none.fl_str_mv Baquero Montoya, Carolina
Gil Rodríguez, María Concepción
Hernández Marcos, María
Teresa Rodrigo, María Esperanza
Vicente Gabas, Alicia
Bernal, María Luisa
Casale, Cesar Horacio
Bueno Lozano, Gloria
Bueno Martínez, Inés
Queralt, Ethel
Villa, Olaya
Hernando Davalillo, Cristina
Armengol, Lluís
Gómez Puertas, Paulino
Puisac, Beatriz
Selicorni, Angelo
Ramos, Feliciano J.
Pié, Juan
author Baquero Montoya, Carolina
author_facet Baquero Montoya, Carolina
Gil Rodríguez, María Concepción
Hernández Marcos, María
Teresa Rodrigo, María Esperanza
Vicente Gabas, Alicia
Bernal, María Luisa
Casale, Cesar Horacio
Bueno Lozano, Gloria
Bueno Martínez, Inés
Queralt, Ethel
Villa, Olaya
Hernando Davalillo, Cristina
Armengol, Lluís
Gómez Puertas, Paulino
Puisac, Beatriz
Selicorni, Angelo
Ramos, Feliciano J.
Pié, Juan
author_role author
author2 Gil Rodríguez, María Concepción
Hernández Marcos, María
Teresa Rodrigo, María Esperanza
Vicente Gabas, Alicia
Bernal, María Luisa
Casale, Cesar Horacio
Bueno Lozano, Gloria
Bueno Martínez, Inés
Queralt, Ethel
Villa, Olaya
Hernando Davalillo, Cristina
Armengol, Lluís
Gómez Puertas, Paulino
Puisac, Beatriz
Selicorni, Angelo
Ramos, Feliciano J.
Pié, Juan
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv BHLHA9 DUPLICATION
CDLS
CORNELIA DE LANGE SYNDROME
EXOME SEQUENCING
HEAT REPEAT
IPSILATERAL
MUSCULOSKELETAL INVOLVEMENT
NIPBL MUTATION
topic BHLHA9 DUPLICATION
CDLS
CORNELIA DE LANGE SYNDROME
EXOME SEQUENCING
HEAT REPEAT
IPSILATERAL
MUSCULOSKELETAL INVOLVEMENT
NIPBL MUTATION
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Cornelia de Lange Syndrome (CdLS) is a congenital autosomal dominant (NIPBL, SMC3 and RAD21) or X-linked (SMC1A and HDAC8) disorder characterized by facial dysmorphism, pre and postnatal growth retardation, developmental delay and/or intellectual disability, and multiorgan involvement. Musculoskeletal malformations are usually bilateral and affect mainly the upper limbs; the range goes from brachyclinodactyly to severe reduction defects. Instead lower extremities are usually less and mildly involved. Here, we report on a 3-year-old Senegalese boy with typical craniofacial CdLS features, pre and postnatal growth retardation, atrial septal defect, developmental delay and right ipsilateral limb malformations, consistent with oligodactyly of the 3rd and 4th fingers, tibial agenesis and fibula hypoplasia. Exome sequencing and Sanger sequencing showed a novel missense mutation in NIPBL gene (c.6647A>G; p.(Tyr2216Cys)), which affects a conserved residue located within NIPBL HEAT repeat elements. Pyrosequencing analysis of NIPBL gene, disclosed similar levels of wild-type and mutated alleles in DNA and RNA samples from all tissues analyzed (oral mucosa epithelial cells, peripheral blood leukocytes and fibroblasts). These findings indicated the absence of somatic mosaicism, despite of the segmental asymmetry of the limbs, and confirmed biallelic expression for NIPBL transcripts, respectively. Additionally, conditions like Split-hand/foot malformation with long-bone deficiency secondary to duplication of BHLHA9 gene have been ruled out by the array-CGH and MLPA analysis. To our knowledge, this is the first CdLS patient described with major ipsilateral malformations of both the upper and lower extremities, that even though this finding could be due to a random event, expands the spectrum of limb reduction defects in CdLS.
Fil: Baquero Montoya, Carolina. Universidad de Zaragoza; España. Hospital Pablo Tobón Uribe; Colombia
Fil: Gil Rodríguez, María Concepción. Universidad de Zaragoza; España
Fil: Hernández Marcos, María. Universidad de Zaragoza; España
Fil: Teresa Rodrigo, María Esperanza. Universidad de Zaragoza; España
Fil: Vicente Gabas, Alicia. Universidad de Zaragoza; España. Hospital Clínico Universitario “Lozano Blesa”; España
Fil: Bernal, María Luisa. Universidad de Zaragoza; España
Fil: Casale, Cesar Horacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Departamento de Biología Molecular; Argentina
Fil: Bueno Lozano, Gloria. Hospital Clínico Universitario “Lozano Blesa”; España
Fil: Bueno Martínez, Inés. Universidad de Zaragoza; España. Hospital Clínico Universitario “Lozano Blesa”; España
Fil: Queralt, Ethel. Universidad de Barcelona. Hospital Duran I Reynals. Instituto de Investigación Biomédica de Bellvitge; España
Fil: Villa, Olaya. Quantitative Genomic Medicine Laboratories; España
Fil: Hernando Davalillo, Cristina. Quantitative Genomic Medicine Laboratories; España
Fil: Armengol, Lluís. Quantitative Genomic Medicine Laboratories; España
Fil: Gómez Puertas, Paulino. Centro de Biología Molecular Severo Ochoa; España
Fil: Puisac, Beatriz. Universidad de Zaragoza; España
Fil: Selicorni, Angelo. University of Milano-Bicocca; Italia
Fil: Ramos, Feliciano J.. Universidad de Zaragoza; España. Hospital Clínico Universitario “Lozano Blesa”; España
Fil: Pié, Juan. Universidad de Zaragoza; España
description Cornelia de Lange Syndrome (CdLS) is a congenital autosomal dominant (NIPBL, SMC3 and RAD21) or X-linked (SMC1A and HDAC8) disorder characterized by facial dysmorphism, pre and postnatal growth retardation, developmental delay and/or intellectual disability, and multiorgan involvement. Musculoskeletal malformations are usually bilateral and affect mainly the upper limbs; the range goes from brachyclinodactyly to severe reduction defects. Instead lower extremities are usually less and mildly involved. Here, we report on a 3-year-old Senegalese boy with typical craniofacial CdLS features, pre and postnatal growth retardation, atrial septal defect, developmental delay and right ipsilateral limb malformations, consistent with oligodactyly of the 3rd and 4th fingers, tibial agenesis and fibula hypoplasia. Exome sequencing and Sanger sequencing showed a novel missense mutation in NIPBL gene (c.6647A>G; p.(Tyr2216Cys)), which affects a conserved residue located within NIPBL HEAT repeat elements. Pyrosequencing analysis of NIPBL gene, disclosed similar levels of wild-type and mutated alleles in DNA and RNA samples from all tissues analyzed (oral mucosa epithelial cells, peripheral blood leukocytes and fibroblasts). These findings indicated the absence of somatic mosaicism, despite of the segmental asymmetry of the limbs, and confirmed biallelic expression for NIPBL transcripts, respectively. Additionally, conditions like Split-hand/foot malformation with long-bone deficiency secondary to duplication of BHLHA9 gene have been ruled out by the array-CGH and MLPA analysis. To our knowledge, this is the first CdLS patient described with major ipsilateral malformations of both the upper and lower extremities, that even though this finding could be due to a random event, expands the spectrum of limb reduction defects in CdLS.
publishDate 2014
dc.date.none.fl_str_mv 2014-04
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/11336/180663
Baquero Montoya, Carolina; Gil Rodríguez, María Concepción; Hernández Marcos, María; Teresa Rodrigo, María Esperanza; Vicente Gabas, Alicia; et al.; Severe ipsilateral musculoskeletal involvement in a Cornelia de Lange patient with a novel NIPBL mutation; Elsevier Science; European Journal Of Medical Genetics; 57; 9; 4-2014; 503-509
1769-7212
1878-0849
CONICET Digital
CONICET
url http://hdl.handle.net/11336/180663
identifier_str_mv Baquero Montoya, Carolina; Gil Rodríguez, María Concepción; Hernández Marcos, María; Teresa Rodrigo, María Esperanza; Vicente Gabas, Alicia; et al.; Severe ipsilateral musculoskeletal involvement in a Cornelia de Lange patient with a novel NIPBL mutation; Elsevier Science; European Journal Of Medical Genetics; 57; 9; 4-2014; 503-509
1769-7212
1878-0849
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/ 10.1016/j.ejmg.2014.05.006
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S1769721214001189
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier Science
publisher.none.fl_str_mv Elsevier Science
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_ 1844613771034624000
score 13.070432