A novel nonsense mutation of EXT1 gene in an Argentinian patient with Multiple Hereditary Exostoses

Autores
Delgado, María Andrea; Sarrión, Patricia; Azar, Nydia Beatríz; Zecchini, Lorena del Valle; Robledo, Hector Hugo; Segura, Florencio Vicente; Balcells, Susana; Grinberg Vaisman, Daniel Raúl; Dodelson de Kremer, Raquel; Asteggiano, Carla Gabriela
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Multiple hereditary exostoses (MHE), also known as multiple osteochondromatosis, is an autosomal-dominant O-linked glycosylation disorder recently classified as EXT1/EXT2-CDG in the congenital disorder of glycosylation (CDG)nomenclature. MHE is characterized by the presence of multiple cartilage-capped tumors,called “osteochondromas,” which usually develop in the juxta-epiphyseal regions of the long bones. The prevalence of MHE is estimated at 1:50,000 in the general population1,2. The Online Mendelian Inheritance in Man (OMIM) database classified it as either 133700 or 133701, according to whether the mutations occurred in the EXT1 or the EXT2 gene. These genes are located at 8q24 and 11p11-11p12, respectively, and they encode the copolymerases responsible for heparan sulfate biosynthesis. EXT1 and EXT2 are tumor suppressor genes of the EXT gene family. The EXT1 gene contains eleven exons with a coding region of 2238 base pairs (bp), and the EXT2 gene contains sixteen exons with a coding region of 2154 bp3-6. These genes encode two glycosyltransferases involved in heparan sulphate biosynthesis, exostosin-1 (EXT1) (EC2.4.1.224)and exostosin-2 (EXT2) (EC2.4.1.225), whose impairment leads to the formation of exostoses4,7-9. Inactivating mutations (nonsense, frameshift, and splice site mutations) in EXT1 and EXT2 genes represent the majority of mutations that cause MHE. An overview of the reported variants is provided by the online Multiple Osteochondroma Mutation Database10. The most important complication of MHE is the malignant transformation of osteochondroma to chondrosarcoma, which is estimated to occur in 0.5% to 5% of patients6. Chondrosarcomas arise de novo (primary) or as a result of a preexistingcartilage lesion (secondary). The biological aggressiveness of chondrosarcomas can be predicted by means of a histological grading system (grade I to grade III), based on three parameters: cellularity, degree of nuclear atypia, and mitotic activity11,12.In our case report, we investigated the clinical, radiographic, and genetic aspects of a patient with MHE with a severe phenotype and malignant transformation to chondrosarcoma.
Fil: Delgado, María Andrea. Gobierno de la Provincia de Córdoba. Ministerio de Salud. Hospital de Niños de la Santísima Trinidad; Argentina
Fil: Sarrión, Patricia. Universidad de Barcelona; España
Fil: Azar, Nydia Beatríz. Gobierno de la Provincia de Córdoba. Ministerio de Salud. Hospital de Niños de la Santísima Trinidad; Argentina
Fil: Zecchini, Lorena del Valle. Gobierno de la Provincia de Córdoba. Ministerio de Salud. Hospital de Niños de la Santísima Trinidad; Argentina
Fil: Robledo, Hector Hugo. Gobierno de la Provincia de Córdoba. Ministerio de Salud. Hospital de Niños de la Santísima Trinidad; Argentina
Fil: Segura, Florencio Vicente. Gobierno de la Provincia de Córdoba. Ministerio de Salud. Hospital de Niños de la Santísima Trinidad; Argentina
Fil: Balcells, Susana. Universidad de Barcelona; España
Fil: Grinberg Vaisman, Daniel Raúl. Universidad de Barcelona; España
Fil: Dodelson de Kremer, Raquel. Gobierno de la Provincia de Córdoba. Ministerio de Salud. Hospital de Niños de la Santísima Trinidad; Argentina
Fil: Asteggiano, Carla Gabriela. Gobierno de la Provincia de Córdoba. Ministerio de Salud. Hospital de Niños de la Santísima Trinidad; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Córdoba; Argentina. Universidad Católica de Córdoba; Argentina
Materia
Multiple Osteochondromatosis
O-glycosylation
EXT1/EXT2-CDG
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:11336/197999
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/197999
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling A novel nonsense mutation of EXT1 gene in an Argentinian patient with Multiple Hereditary ExostosesDelgado, María AndreaSarrión, PatriciaAzar, Nydia BeatrízZecchini, Lorena del ValleRobledo, Hector HugoSegura, Florencio VicenteBalcells, SusanaGrinberg Vaisman, Daniel RaúlDodelson de Kremer, RaquelAsteggiano, Carla GabrielaMultiple OsteochondromatosisO-glycosylationEXT1/EXT2-CDGhttps://purl.org/becyt/ford/3.5https://purl.org/becyt/ford/3Multiple hereditary exostoses (MHE), also known as multiple osteochondromatosis, is an autosomal-dominant O-linked glycosylation disorder recently classified as EXT1/EXT2-CDG in the congenital disorder of glycosylation (CDG)nomenclature. MHE is characterized by the presence of multiple cartilage-capped tumors,called “osteochondromas,” which usually develop in the juxta-epiphyseal regions of the long bones. The prevalence of MHE is estimated at 1:50,000 in the general population1,2. The Online Mendelian Inheritance in Man (OMIM) database classified it as either 133700 or 133701, according to whether the mutations occurred in the EXT1 or the EXT2 gene. These genes are located at 8q24 and 11p11-11p12, respectively, and they encode the copolymerases responsible for heparan sulfate biosynthesis. EXT1 and EXT2 are tumor suppressor genes of the EXT gene family. The EXT1 gene contains eleven exons with a coding region of 2238 base pairs (bp), and the EXT2 gene contains sixteen exons with a coding region of 2154 bp3-6. These genes encode two glycosyltransferases involved in heparan sulphate biosynthesis, exostosin-1 (EXT1) (EC2.4.1.224)and exostosin-2 (EXT2) (EC2.4.1.225), whose impairment leads to the formation of exostoses4,7-9. Inactivating mutations (nonsense, frameshift, and splice site mutations) in EXT1 and EXT2 genes represent the majority of mutations that cause MHE. An overview of the reported variants is provided by the online Multiple Osteochondroma Mutation Database10. The most important complication of MHE is the malignant transformation of osteochondroma to chondrosarcoma, which is estimated to occur in 0.5% to 5% of patients6. Chondrosarcomas arise de novo (primary) or as a result of a preexistingcartilage lesion (secondary). The biological aggressiveness of chondrosarcomas can be predicted by means of a histological grading system (grade I to grade III), based on three parameters: cellularity, degree of nuclear atypia, and mitotic activity11,12.In our case report, we investigated the clinical, radiographic, and genetic aspects of a patient with MHE with a severe phenotype and malignant transformation to chondrosarcoma.Fil: Delgado, María Andrea. Gobierno de la Provincia de Córdoba. Ministerio de Salud. Hospital de Niños de la Santísima Trinidad; ArgentinaFil: Sarrión, Patricia. Universidad de Barcelona; EspañaFil: Azar, Nydia Beatríz. Gobierno de la Provincia de Córdoba. Ministerio de Salud. Hospital de Niños de la Santísima Trinidad; ArgentinaFil: Zecchini, Lorena del Valle. Gobierno de la Provincia de Córdoba. Ministerio de Salud. Hospital de Niños de la Santísima Trinidad; ArgentinaFil: Robledo, Hector Hugo. Gobierno de la Provincia de Córdoba. Ministerio de Salud. Hospital de Niños de la Santísima Trinidad; ArgentinaFil: Segura, Florencio Vicente. Gobierno de la Provincia de Córdoba. Ministerio de Salud. Hospital de Niños de la Santísima Trinidad; ArgentinaFil: Balcells, Susana. Universidad de Barcelona; EspañaFil: Grinberg Vaisman, Daniel Raúl. Universidad de Barcelona; EspañaFil: Dodelson de Kremer, Raquel. Gobierno de la Provincia de Córdoba. Ministerio de Salud. Hospital de Niños de la Santísima Trinidad; ArgentinaFil: Asteggiano, Carla Gabriela. Gobierno de la Provincia de Córdoba. Ministerio de Salud. Hospital de Niños de la Santísima Trinidad; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Córdoba; Argentina. Universidad Católica de Córdoba; ArgentinaJournal Bone Joint Surgery Inc2012-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/197999Delgado, María Andrea; Sarrión, Patricia; Azar, Nydia Beatríz; Zecchini, Lorena del Valle; Robledo, Hector Hugo; et al.; A novel nonsense mutation of EXT1 gene in an Argentinian patient with Multiple Hereditary Exostoses; Journal Bone Joint Surgery Inc; Journal Of Bone And Joint Surgery-american Volume; 94; 11; 6-2012; 761-7660375-92290021-9355CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.2106/JBJS.J.01920info:eu-repo/semantics/altIdentifier/url/https://journals.lww.com/jbjsjournal/Citation/2012/06060/A_Novel_Nonsense_Mutation_of_the_EXT1_Gene_in_an.15.aspxinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:11:55Zoai:ri.conicet.gov.ar:11336/197999instacron: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 10:11:56.053CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv A novel nonsense mutation of EXT1 gene in an Argentinian patient with Multiple Hereditary Exostoses
title A novel nonsense mutation of EXT1 gene in an Argentinian patient with Multiple Hereditary Exostoses
spellingShingle A novel nonsense mutation of EXT1 gene in an Argentinian patient with Multiple Hereditary Exostoses
Delgado, María Andrea
Multiple Osteochondromatosis
O-glycosylation
EXT1/EXT2-CDG
title_short A novel nonsense mutation of EXT1 gene in an Argentinian patient with Multiple Hereditary Exostoses
title_full A novel nonsense mutation of EXT1 gene in an Argentinian patient with Multiple Hereditary Exostoses
title_fullStr A novel nonsense mutation of EXT1 gene in an Argentinian patient with Multiple Hereditary Exostoses
title_full_unstemmed A novel nonsense mutation of EXT1 gene in an Argentinian patient with Multiple Hereditary Exostoses
title_sort A novel nonsense mutation of EXT1 gene in an Argentinian patient with Multiple Hereditary Exostoses
dc.creator.none.fl_str_mv Delgado, María Andrea
Sarrión, Patricia
Azar, Nydia Beatríz
Zecchini, Lorena del Valle
Robledo, Hector Hugo
Segura, Florencio Vicente
Balcells, Susana
Grinberg Vaisman, Daniel Raúl
Dodelson de Kremer, Raquel
Asteggiano, Carla Gabriela
author Delgado, María Andrea
author_facet Delgado, María Andrea
Sarrión, Patricia
Azar, Nydia Beatríz
Zecchini, Lorena del Valle
Robledo, Hector Hugo
Segura, Florencio Vicente
Balcells, Susana
Grinberg Vaisman, Daniel Raúl
Dodelson de Kremer, Raquel
Asteggiano, Carla Gabriela
author_role author
author2 Sarrión, Patricia
Azar, Nydia Beatríz
Zecchini, Lorena del Valle
Robledo, Hector Hugo
Segura, Florencio Vicente
Balcells, Susana
Grinberg Vaisman, Daniel Raúl
Dodelson de Kremer, Raquel
Asteggiano, Carla Gabriela
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Multiple Osteochondromatosis
O-glycosylation
EXT1/EXT2-CDG
topic Multiple Osteochondromatosis
O-glycosylation
EXT1/EXT2-CDG
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.5
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Multiple hereditary exostoses (MHE), also known as multiple osteochondromatosis, is an autosomal-dominant O-linked glycosylation disorder recently classified as EXT1/EXT2-CDG in the congenital disorder of glycosylation (CDG)nomenclature. MHE is characterized by the presence of multiple cartilage-capped tumors,called “osteochondromas,” which usually develop in the juxta-epiphyseal regions of the long bones. The prevalence of MHE is estimated at 1:50,000 in the general population1,2. The Online Mendelian Inheritance in Man (OMIM) database classified it as either 133700 or 133701, according to whether the mutations occurred in the EXT1 or the EXT2 gene. These genes are located at 8q24 and 11p11-11p12, respectively, and they encode the copolymerases responsible for heparan sulfate biosynthesis. EXT1 and EXT2 are tumor suppressor genes of the EXT gene family. The EXT1 gene contains eleven exons with a coding region of 2238 base pairs (bp), and the EXT2 gene contains sixteen exons with a coding region of 2154 bp3-6. These genes encode two glycosyltransferases involved in heparan sulphate biosynthesis, exostosin-1 (EXT1) (EC2.4.1.224)and exostosin-2 (EXT2) (EC2.4.1.225), whose impairment leads to the formation of exostoses4,7-9. Inactivating mutations (nonsense, frameshift, and splice site mutations) in EXT1 and EXT2 genes represent the majority of mutations that cause MHE. An overview of the reported variants is provided by the online Multiple Osteochondroma Mutation Database10. The most important complication of MHE is the malignant transformation of osteochondroma to chondrosarcoma, which is estimated to occur in 0.5% to 5% of patients6. Chondrosarcomas arise de novo (primary) or as a result of a preexistingcartilage lesion (secondary). The biological aggressiveness of chondrosarcomas can be predicted by means of a histological grading system (grade I to grade III), based on three parameters: cellularity, degree of nuclear atypia, and mitotic activity11,12.In our case report, we investigated the clinical, radiographic, and genetic aspects of a patient with MHE with a severe phenotype and malignant transformation to chondrosarcoma.
Fil: Delgado, María Andrea. Gobierno de la Provincia de Córdoba. Ministerio de Salud. Hospital de Niños de la Santísima Trinidad; Argentina
Fil: Sarrión, Patricia. Universidad de Barcelona; España
Fil: Azar, Nydia Beatríz. Gobierno de la Provincia de Córdoba. Ministerio de Salud. Hospital de Niños de la Santísima Trinidad; Argentina
Fil: Zecchini, Lorena del Valle. Gobierno de la Provincia de Córdoba. Ministerio de Salud. Hospital de Niños de la Santísima Trinidad; Argentina
Fil: Robledo, Hector Hugo. Gobierno de la Provincia de Córdoba. Ministerio de Salud. Hospital de Niños de la Santísima Trinidad; Argentina
Fil: Segura, Florencio Vicente. Gobierno de la Provincia de Córdoba. Ministerio de Salud. Hospital de Niños de la Santísima Trinidad; Argentina
Fil: Balcells, Susana. Universidad de Barcelona; España
Fil: Grinberg Vaisman, Daniel Raúl. Universidad de Barcelona; España
Fil: Dodelson de Kremer, Raquel. Gobierno de la Provincia de Córdoba. Ministerio de Salud. Hospital de Niños de la Santísima Trinidad; Argentina
Fil: Asteggiano, Carla Gabriela. Gobierno de la Provincia de Córdoba. Ministerio de Salud. Hospital de Niños de la Santísima Trinidad; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Córdoba; Argentina. Universidad Católica de Córdoba; Argentina
description Multiple hereditary exostoses (MHE), also known as multiple osteochondromatosis, is an autosomal-dominant O-linked glycosylation disorder recently classified as EXT1/EXT2-CDG in the congenital disorder of glycosylation (CDG)nomenclature. MHE is characterized by the presence of multiple cartilage-capped tumors,called “osteochondromas,” which usually develop in the juxta-epiphyseal regions of the long bones. The prevalence of MHE is estimated at 1:50,000 in the general population1,2. The Online Mendelian Inheritance in Man (OMIM) database classified it as either 133700 or 133701, according to whether the mutations occurred in the EXT1 or the EXT2 gene. These genes are located at 8q24 and 11p11-11p12, respectively, and they encode the copolymerases responsible for heparan sulfate biosynthesis. EXT1 and EXT2 are tumor suppressor genes of the EXT gene family. The EXT1 gene contains eleven exons with a coding region of 2238 base pairs (bp), and the EXT2 gene contains sixteen exons with a coding region of 2154 bp3-6. These genes encode two glycosyltransferases involved in heparan sulphate biosynthesis, exostosin-1 (EXT1) (EC2.4.1.224)and exostosin-2 (EXT2) (EC2.4.1.225), whose impairment leads to the formation of exostoses4,7-9. Inactivating mutations (nonsense, frameshift, and splice site mutations) in EXT1 and EXT2 genes represent the majority of mutations that cause MHE. An overview of the reported variants is provided by the online Multiple Osteochondroma Mutation Database10. The most important complication of MHE is the malignant transformation of osteochondroma to chondrosarcoma, which is estimated to occur in 0.5% to 5% of patients6. Chondrosarcomas arise de novo (primary) or as a result of a preexistingcartilage lesion (secondary). The biological aggressiveness of chondrosarcomas can be predicted by means of a histological grading system (grade I to grade III), based on three parameters: cellularity, degree of nuclear atypia, and mitotic activity11,12.In our case report, we investigated the clinical, radiographic, and genetic aspects of a patient with MHE with a severe phenotype and malignant transformation to chondrosarcoma.
publishDate 2012
dc.date.none.fl_str_mv 2012-06
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/11336/197999
Delgado, María Andrea; Sarrión, Patricia; Azar, Nydia Beatríz; Zecchini, Lorena del Valle; Robledo, Hector Hugo; et al.; A novel nonsense mutation of EXT1 gene in an Argentinian patient with Multiple Hereditary Exostoses; Journal Bone Joint Surgery Inc; Journal Of Bone And Joint Surgery-american Volume; 94; 11; 6-2012; 761-766
0375-9229
0021-9355
CONICET Digital
CONICET
url http://hdl.handle.net/11336/197999
identifier_str_mv Delgado, María Andrea; Sarrión, Patricia; Azar, Nydia Beatríz; Zecchini, Lorena del Valle; Robledo, Hector Hugo; et al.; A novel nonsense mutation of EXT1 gene in an Argentinian patient with Multiple Hereditary Exostoses; Journal Bone Joint Surgery Inc; Journal Of Bone And Joint Surgery-american Volume; 94; 11; 6-2012; 761-766
0375-9229
0021-9355
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.2106/JBJS.J.01920
info:eu-repo/semantics/altIdentifier/url/https://journals.lww.com/jbjsjournal/Citation/2012/06060/A_Novel_Nonsense_Mutation_of_the_EXT1_Gene_in_an.15.aspx
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 Journal Bone Joint Surgery Inc
publisher.none.fl_str_mv Journal Bone Joint Surgery 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

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