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
.jpg)
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/180663
Ver los metadatos del registro completo
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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 Técnicas2025-10-22T11:29:10Zoai: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:34982025-10-22 11:29:11.203CONICET 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 |
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info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
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article |
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publishedVersion |
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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 |
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eng |
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eng |
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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 |
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openAccess |
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Elsevier Science |
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Elsevier Science |
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CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
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dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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