Clinical and Genetic Analysis of Multiple Osteochondromas in A Cohort of Argentine Patients

Autores
Caino, Silvia Alejandra; Cubilla, Marisa Angelica; Alba, Romina; Obregón, María Gabriela; Fano, Virginia; Gómez, Abel; Zecchini, Lorena del Valle; Lapunzina, Pablo; Aza Carmona, Miriam; Heath, Karen Elise; Asteggiano, Carla Gabriela
Año de publicación
2022
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Multiple Osteochondromatosis (MO, MIM 133700 & 133701), an autosomal dominant O-glycosylation disorder (EXT1/EXT2-CDG), can be associated with a reduction in skeletal growth, bony deformity, restricted joint motion, shortened stature and pathogenic variants in two tumor suppressor genes, EXT1 and EXT2. In this work, we report a cross-sectional study including 35 index patients and 20 affected family members. Clinical phenotyping of all 55 affected cases was obtained, but genetic studies were performed only in 35 indexes. Of these, a total of 40% (n = 14) had a family history of MO. Clinical severity scores were class I in 34% (n:18), class II in 24.5% (n:13) and class III in 41.5% (n:22). Pathogenic variants were identified in 83% (29/35) probands. We detected 18 (62%) in EXT1 and 11 (38%) in EXT2. Patients with EXT1 variants showed a height z-score of 1.03 SD lower than those with EXT2 variants and greater clinical severity (II-III vs. I). Interestingly, three patients showed intellectual impairment, two patients showed a dual diagnosis, one Turner Syndrome and one hypochondroplasia. This study improves knowledge of MO, reporting new pathogenic variants and forwarding the worldwide collaboration necessary to promote the inclusion of patients into future biologically based therapeutics.
Fil: Caino, Silvia Alejandra. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Cubilla, Marisa Angelica. Gobierno de la Provincia de Cordoba. Ministerio de Salud. Hospital de Niños de la Santísima Trinidad.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina
Fil: Alba, Romina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Obregón, María Gabriela. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Fano, Virginia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Gómez, Abel. Gobierno de la Provincia de Cordoba. Ministerio de Salud. Hospital de Niños de la Santísima Trinidad.; Argentina
Fil: Zecchini, Lorena del Valle. Gobierno de la Provincia de Cordoba. Ministerio de Salud. Hospital de Niños de la Santísima Trinidad.; Argentina
Fil: Lapunzina, Pablo. No especifíca;
Fil: Aza Carmona, Miriam. No especifíca;
Fil: Heath, Karen Elise. No especifíca;
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. Centro Científico Tecnológico Conicet - Córdoba; Argentina. Universidad Católica de Córdoba; Argentina
Materia
EXT1/EXT2-CDG
MULTIPLE EXOSTOSIS
MULTIPLE OSTEOCHONDROMATOSIS
O-GLYCOSYLATION DISORDERS
OSTEOCHONDROMA
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/215310
Acceder
id CONICETDig_296c47906603357cb715da6a3687f7d8
oai_identifier_str oai:ri.conicet.gov.ar:11336/215310
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Clinical and Genetic Analysis of Multiple Osteochondromas in A Cohort of Argentine PatientsCaino, Silvia AlejandraCubilla, Marisa AngelicaAlba, RominaObregón, María GabrielaFano, VirginiaGómez, AbelZecchini, Lorena del ValleLapunzina, PabloAza Carmona, MiriamHeath, Karen EliseAsteggiano, Carla GabrielaEXT1/EXT2-CDGMULTIPLE EXOSTOSISMULTIPLE OSTEOCHONDROMATOSISO-GLYCOSYLATION DISORDERSOSTEOCHONDROMAhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Multiple Osteochondromatosis (MO, MIM 133700 & 133701), an autosomal dominant O-glycosylation disorder (EXT1/EXT2-CDG), can be associated with a reduction in skeletal growth, bony deformity, restricted joint motion, shortened stature and pathogenic variants in two tumor suppressor genes, EXT1 and EXT2. In this work, we report a cross-sectional study including 35 index patients and 20 affected family members. Clinical phenotyping of all 55 affected cases was obtained, but genetic studies were performed only in 35 indexes. Of these, a total of 40% (n = 14) had a family history of MO. Clinical severity scores were class I in 34% (n:18), class II in 24.5% (n:13) and class III in 41.5% (n:22). Pathogenic variants were identified in 83% (29/35) probands. We detected 18 (62%) in EXT1 and 11 (38%) in EXT2. Patients with EXT1 variants showed a height z-score of 1.03 SD lower than those with EXT2 variants and greater clinical severity (II-III vs. I). Interestingly, three patients showed intellectual impairment, two patients showed a dual diagnosis, one Turner Syndrome and one hypochondroplasia. This study improves knowledge of MO, reporting new pathogenic variants and forwarding the worldwide collaboration necessary to promote the inclusion of patients into future biologically based therapeutics.Fil: Caino, Silvia Alejandra. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cubilla, Marisa Angelica. Gobierno de la Provincia de Cordoba. Ministerio de Salud. Hospital de Niños de la Santísima Trinidad.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Alba, Romina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Obregón, María Gabriela. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Fano, Virginia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Gómez, Abel. Gobierno de la Provincia de Cordoba. Ministerio de Salud. Hospital de Niños de la Santísima Trinidad.; ArgentinaFil: Zecchini, Lorena del Valle. Gobierno de la Provincia de Cordoba. Ministerio de Salud. Hospital de Niños de la Santísima Trinidad.; ArgentinaFil: Lapunzina, Pablo. No especifíca;Fil: Aza Carmona, Miriam. No especifíca;Fil: Heath, Karen Elise. No especifíca;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. Centro Científico Tecnológico Conicet - Córdoba; Argentina. Universidad Católica de Córdoba; ArgentinaMDPI2022-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/215310Caino, Silvia Alejandra; Cubilla, Marisa Angelica; Alba, Romina; Obregón, María Gabriela; Fano, Virginia; et al.; Clinical and Genetic Analysis of Multiple Osteochondromas in A Cohort of Argentine Patients; MDPI; Genes; 13; 11; 11-2022; 1-142073-4425CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.3390/genes13112063info:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/2073-4425/13/11/2063info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:10:40Zoai:ri.conicet.gov.ar:11336/215310instacron: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 10:10:40.351CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Clinical and Genetic Analysis of Multiple Osteochondromas in A Cohort of Argentine Patients
title Clinical and Genetic Analysis of Multiple Osteochondromas in A Cohort of Argentine Patients
spellingShingle Clinical and Genetic Analysis of Multiple Osteochondromas in A Cohort of Argentine Patients
Caino, Silvia Alejandra
EXT1/EXT2-CDG
MULTIPLE EXOSTOSIS
MULTIPLE OSTEOCHONDROMATOSIS
O-GLYCOSYLATION DISORDERS
OSTEOCHONDROMA
title_short Clinical and Genetic Analysis of Multiple Osteochondromas in A Cohort of Argentine Patients
title_full Clinical and Genetic Analysis of Multiple Osteochondromas in A Cohort of Argentine Patients
title_fullStr Clinical and Genetic Analysis of Multiple Osteochondromas in A Cohort of Argentine Patients
title_full_unstemmed Clinical and Genetic Analysis of Multiple Osteochondromas in A Cohort of Argentine Patients
title_sort Clinical and Genetic Analysis of Multiple Osteochondromas in A Cohort of Argentine Patients
dc.creator.none.fl_str_mv Caino, Silvia Alejandra
Cubilla, Marisa Angelica
Alba, Romina
Obregón, María Gabriela
Fano, Virginia
Gómez, Abel
Zecchini, Lorena del Valle
Lapunzina, Pablo
Aza Carmona, Miriam
Heath, Karen Elise
Asteggiano, Carla Gabriela
author Caino, Silvia Alejandra
author_facet Caino, Silvia Alejandra
Cubilla, Marisa Angelica
Alba, Romina
Obregón, María Gabriela
Fano, Virginia
Gómez, Abel
Zecchini, Lorena del Valle
Lapunzina, Pablo
Aza Carmona, Miriam
Heath, Karen Elise
Asteggiano, Carla Gabriela
author_role author
author2 Cubilla, Marisa Angelica
Alba, Romina
Obregón, María Gabriela
Fano, Virginia
Gómez, Abel
Zecchini, Lorena del Valle
Lapunzina, Pablo
Aza Carmona, Miriam
Heath, Karen Elise
Asteggiano, Carla Gabriela
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv EXT1/EXT2-CDG
MULTIPLE EXOSTOSIS
MULTIPLE OSTEOCHONDROMATOSIS
O-GLYCOSYLATION DISORDERS
OSTEOCHONDROMA
topic EXT1/EXT2-CDG
MULTIPLE EXOSTOSIS
MULTIPLE OSTEOCHONDROMATOSIS
O-GLYCOSYLATION DISORDERS
OSTEOCHONDROMA
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Multiple Osteochondromatosis (MO, MIM 133700 & 133701), an autosomal dominant O-glycosylation disorder (EXT1/EXT2-CDG), can be associated with a reduction in skeletal growth, bony deformity, restricted joint motion, shortened stature and pathogenic variants in two tumor suppressor genes, EXT1 and EXT2. In this work, we report a cross-sectional study including 35 index patients and 20 affected family members. Clinical phenotyping of all 55 affected cases was obtained, but genetic studies were performed only in 35 indexes. Of these, a total of 40% (n = 14) had a family history of MO. Clinical severity scores were class I in 34% (n:18), class II in 24.5% (n:13) and class III in 41.5% (n:22). Pathogenic variants were identified in 83% (29/35) probands. We detected 18 (62%) in EXT1 and 11 (38%) in EXT2. Patients with EXT1 variants showed a height z-score of 1.03 SD lower than those with EXT2 variants and greater clinical severity (II-III vs. I). Interestingly, three patients showed intellectual impairment, two patients showed a dual diagnosis, one Turner Syndrome and one hypochondroplasia. This study improves knowledge of MO, reporting new pathogenic variants and forwarding the worldwide collaboration necessary to promote the inclusion of patients into future biologically based therapeutics.
Fil: Caino, Silvia Alejandra. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Cubilla, Marisa Angelica. Gobierno de la Provincia de Cordoba. Ministerio de Salud. Hospital de Niños de la Santísima Trinidad.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina
Fil: Alba, Romina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Obregón, María Gabriela. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Fano, Virginia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Gómez, Abel. Gobierno de la Provincia de Cordoba. Ministerio de Salud. Hospital de Niños de la Santísima Trinidad.; Argentina
Fil: Zecchini, Lorena del Valle. Gobierno de la Provincia de Cordoba. Ministerio de Salud. Hospital de Niños de la Santísima Trinidad.; Argentina
Fil: Lapunzina, Pablo. No especifíca;
Fil: Aza Carmona, Miriam. No especifíca;
Fil: Heath, Karen Elise. No especifíca;
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. Centro Científico Tecnológico Conicet - Córdoba; Argentina. Universidad Católica de Córdoba; Argentina
description Multiple Osteochondromatosis (MO, MIM 133700 & 133701), an autosomal dominant O-glycosylation disorder (EXT1/EXT2-CDG), can be associated with a reduction in skeletal growth, bony deformity, restricted joint motion, shortened stature and pathogenic variants in two tumor suppressor genes, EXT1 and EXT2. In this work, we report a cross-sectional study including 35 index patients and 20 affected family members. Clinical phenotyping of all 55 affected cases was obtained, but genetic studies were performed only in 35 indexes. Of these, a total of 40% (n = 14) had a family history of MO. Clinical severity scores were class I in 34% (n:18), class II in 24.5% (n:13) and class III in 41.5% (n:22). Pathogenic variants were identified in 83% (29/35) probands. We detected 18 (62%) in EXT1 and 11 (38%) in EXT2. Patients with EXT1 variants showed a height z-score of 1.03 SD lower than those with EXT2 variants and greater clinical severity (II-III vs. I). Interestingly, three patients showed intellectual impairment, two patients showed a dual diagnosis, one Turner Syndrome and one hypochondroplasia. This study improves knowledge of MO, reporting new pathogenic variants and forwarding the worldwide collaboration necessary to promote the inclusion of patients into future biologically based therapeutics.
publishDate 2022
dc.date.none.fl_str_mv 2022-11
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/11336/215310
Caino, Silvia Alejandra; Cubilla, Marisa Angelica; Alba, Romina; Obregón, María Gabriela; Fano, Virginia; et al.; Clinical and Genetic Analysis of Multiple Osteochondromas in A Cohort of Argentine Patients; MDPI; Genes; 13; 11; 11-2022; 1-14
2073-4425
CONICET Digital
CONICET
url http://hdl.handle.net/11336/215310
identifier_str_mv Caino, Silvia Alejandra; Cubilla, Marisa Angelica; Alba, Romina; Obregón, María Gabriela; Fano, Virginia; et al.; Clinical and Genetic Analysis of Multiple Osteochondromas in A Cohort of Argentine Patients; MDPI; Genes; 13; 11; 11-2022; 1-14
2073-4425
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.3390/genes13112063
info:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/2073-4425/13/11/2063
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
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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