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

Autores
Caino, Silvia; Cubilla, Marisa Angelica; Alba, Romina; Obregón, María Gabriela; Fano, Virginia; Gómez, Abel; Zecchini, Lorena del Valle; Lapunzina, Pablo; Aza Carmona, Miriam; Heath, Karen E.; Asteggiano, Carla Gabriela
Año de publicación
2022
Idioma
español castellano
Tipo de recurso
artículo
Estado
versión aceptada
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. Hospital de Pediatría J.P, Garrahan. Servicio de Crecimiento y Desarrollo,; Argentina
Fil: Cubilla, Marisa Angelica. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas; Argentina
Fil: Alba, Romina. Hospital de Pediatría J.P, Garrahan. Servicio de Crecimiento y Desarrollo,; Argentina
Fil: Obregón, María Gabriela. Hospital de Pediatría J.P, Garrahan; Argentina
Fil: Fano, Virginia. Hospital de Pediatría J.P, Garrahan. Servicio de Crecimiento y Desarrollo,; Argentina
Fil: Gómez, Abel. Hospital de Pediatría J.P, Garrahan; Argentina
Fil: Zecchini, Lorena del Valle. Hospital de Niños de la Santísima Trinidad; Argentina
Fil: Lapunzina, Pablo. Hospital Universitario La Paz; España
Fil: Aza Carmona, Miriam. Hospital Universitario La Paz; España
Fil: Heath, Karen E. Hospital Universitario La Paz; España
Fil: Asteggiano, Carla Gabriela. Universidad Católica de Córdoba. Facultad de Ciencias de la Salud; Argentina
Fuente
Caino, Silvia ORCID: https://orcid.org/0000-0002-2602-0793 , Cubilla, Marisa Angelica ORCID: https://orcid.org/0000-0002-9862-8933 , Alba, Romina ORCID: https://orcid.org/0000-0003-1324-8972 , Obregón, María Gabriela ORCID: https://orcid.org/0000-0001-7129-8009 , Fano, Virginia ORCID: https://orcid.org/0000-0003-3311-2220 , Gómez, Abel, Zecchini, Lorena del Valle ORCID: https://orcid.org/0000-0002-2284-3266 , Lapunzina, Pablo ORCID: https://orcid.org/0000-0002-6324-4825 , Aza Carmona, Miriam ORCID: https://orcid.org/0000-0003-4448-9541 , Heath, Karen E. ORCID: https://orcid.org/0000-0002-5816-7044 and Asteggiano, Carla Gabriela ORCID: https://orcid.org/0000-0003-4713-2775 (2022) Clinical and Genetic Analysis of Multiple Osteochondromas in a Cohort of Argentine Patients. Genes (13).
Materia
R Medicina (General)
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/4.0/deed.es
Repositorio
Producción Académica (UCC)
Institución
Universidad Católica de Córdoba
OAI Identificador
oai:pa.bibdigital.uccor.edu.ar:3684
Acceder
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repository_id_str 2718
network_name_str Producción Académica (UCC)
spelling Clinical and Genetic Analysis of Multiple Osteochondromas in a Cohort of Argentine PatientsCaino, SilviaCubilla, Marisa AngelicaAlba, RominaObregón, María GabrielaFano, VirginiaGómez, AbelZecchini, Lorena del ValleLapunzina, PabloAza Carmona, MiriamHeath, Karen E.Asteggiano, Carla GabrielaR Medicina (General)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. Hospital de Pediatría J.P, Garrahan. Servicio de Crecimiento y Desarrollo,; ArgentinaFil: Cubilla, Marisa Angelica. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas; ArgentinaFil: Alba, Romina. Hospital de Pediatría J.P, Garrahan. Servicio de Crecimiento y Desarrollo,; ArgentinaFil: Obregón, María Gabriela. Hospital de Pediatría J.P, Garrahan; ArgentinaFil: Fano, Virginia. Hospital de Pediatría J.P, Garrahan. Servicio de Crecimiento y Desarrollo,; ArgentinaFil: Gómez, Abel. Hospital de Pediatría J.P, Garrahan; ArgentinaFil: Zecchini, Lorena del Valle. Hospital de Niños de la Santísima Trinidad; ArgentinaFil: Lapunzina, Pablo. Hospital Universitario La Paz; EspañaFil: Aza Carmona, Miriam. Hospital Universitario La Paz; EspañaFil: Heath, Karen E. Hospital Universitario La Paz; EspañaFil: Asteggiano, Carla Gabriela. Universidad Católica de Córdoba. Facultad de Ciencias de la Salud; Argentina2022-11-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttp://pa.bibdigital.ucc.edu.ar/3684/1/A_Caino_Cubilla_Alba_Obreg%C3%B3n_Fano_G%C3%B3mez_Zecchini_Lapunzina_AzaCarmona_Heath_Asteggiano.pdf Caino, Silvia ORCID: https://orcid.org/0000-0002-2602-0793 <https://orcid.org/0000-0002-2602-0793>, Cubilla, Marisa Angelica ORCID: https://orcid.org/0000-0002-9862-8933 <https://orcid.org/0000-0002-9862-8933>, Alba, Romina ORCID: https://orcid.org/0000-0003-1324-8972 <https://orcid.org/0000-0003-1324-8972>, Obregón, María Gabriela ORCID: https://orcid.org/0000-0001-7129-8009 <https://orcid.org/0000-0001-7129-8009>, Fano, Virginia ORCID: https://orcid.org/0000-0003-3311-2220 <https://orcid.org/0000-0003-3311-2220>, Gómez, Abel, Zecchini, Lorena del Valle ORCID: https://orcid.org/0000-0002-2284-3266 <https://orcid.org/0000-0002-2284-3266>, Lapunzina, Pablo ORCID: https://orcid.org/0000-0002-6324-4825 <https://orcid.org/0000-0002-6324-4825>, Aza Carmona, Miriam ORCID: https://orcid.org/0000-0003-4448-9541 <https://orcid.org/0000-0003-4448-9541>, Heath, Karen E. ORCID: https://orcid.org/0000-0002-5816-7044 <https://orcid.org/0000-0002-5816-7044> and Asteggiano, Carla Gabriela ORCID: https://orcid.org/0000-0003-4713-2775 <https://orcid.org/0000-0003-4713-2775> (2022) Clinical and Genetic Analysis of Multiple Osteochondromas in a Cohort of Argentine Patients. Genes (13). reponame:Producción Académica (UCC)instname:Universidad Católica de Córdobaspahttp://pa.bibdigital.ucc.edu.ar/3684/https://www.mdpi.com/2073-4425/13/11/2063info:eu-repo/semantics/altIdentifier/doi/https://doi.org/10.3390/genes13112063info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/4.0/deed.es2025-09-29T14:29:39Zoai:pa.bibdigital.uccor.edu.ar:3684instacron:UCCInstitucionalhttp://pa.bibdigital.uccor.edu.ar/Universidad privadaNo correspondehttp://pa.bibdigital.uccor.edu.ar/cgi/oai2bibdir@uccor.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:27182025-09-29 14:29:39.432Producción Académica (UCC) - Universidad Católica de Córdobafalse
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
R Medicina (General)
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
Cubilla, Marisa Angelica
Alba, Romina
Obregón, María Gabriela
Fano, Virginia
Gómez, Abel
Zecchini, Lorena del Valle
Lapunzina, Pablo
Aza Carmona, Miriam
Heath, Karen E.
Asteggiano, Carla Gabriela
author Caino, Silvia
author_facet Caino, Silvia
Cubilla, Marisa Angelica
Alba, Romina
Obregón, María Gabriela
Fano, Virginia
Gómez, Abel
Zecchini, Lorena del Valle
Lapunzina, Pablo
Aza Carmona, Miriam
Heath, Karen E.
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 E.
Asteggiano, Carla Gabriela
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv R Medicina (General)
topic R Medicina (General)
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. Hospital de Pediatría J.P, Garrahan. Servicio de Crecimiento y Desarrollo,; Argentina
Fil: Cubilla, Marisa Angelica. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas; Argentina
Fil: Alba, Romina. Hospital de Pediatría J.P, Garrahan. Servicio de Crecimiento y Desarrollo,; Argentina
Fil: Obregón, María Gabriela. Hospital de Pediatría J.P, Garrahan; Argentina
Fil: Fano, Virginia. Hospital de Pediatría J.P, Garrahan. Servicio de Crecimiento y Desarrollo,; Argentina
Fil: Gómez, Abel. Hospital de Pediatría J.P, Garrahan; Argentina
Fil: Zecchini, Lorena del Valle. Hospital de Niños de la Santísima Trinidad; Argentina
Fil: Lapunzina, Pablo. Hospital Universitario La Paz; España
Fil: Aza Carmona, Miriam. Hospital Universitario La Paz; España
Fil: Heath, Karen E. Hospital Universitario La Paz; España
Fil: Asteggiano, Carla Gabriela. Universidad Católica de Córdoba. Facultad de Ciencias de la Salud; 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 2022-11-07
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv http://pa.bibdigital.ucc.edu.ar/3684/1/A_Caino_Cubilla_Alba_Obreg%C3%B3n_Fano_G%C3%B3mez_Zecchini_Lapunzina_AzaCarmona_Heath_Asteggiano.pdf
url http://pa.bibdigital.ucc.edu.ar/3684/1/A_Caino_Cubilla_Alba_Obreg%C3%B3n_Fano_G%C3%B3mez_Zecchini_Lapunzina_AzaCarmona_Heath_Asteggiano.pdf
dc.language.none.fl_str_mv spa
language spa
dc.relation.none.fl_str_mv http://pa.bibdigital.ucc.edu.ar/3684/
https://www.mdpi.com/2073-4425/13/11/2063
info:eu-repo/semantics/altIdentifier/doi/https://doi.org/10.3390/genes13112063
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/4.0/deed.es
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/4.0/deed.es
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv Caino, Silvia ORCID: https://orcid.org/0000-0002-2602-0793 <https://orcid.org/0000-0002-2602-0793>, Cubilla, Marisa Angelica ORCID: https://orcid.org/0000-0002-9862-8933 <https://orcid.org/0000-0002-9862-8933>, Alba, Romina ORCID: https://orcid.org/0000-0003-1324-8972 <https://orcid.org/0000-0003-1324-8972>, Obregón, María Gabriela ORCID: https://orcid.org/0000-0001-7129-8009 <https://orcid.org/0000-0001-7129-8009>, Fano, Virginia ORCID: https://orcid.org/0000-0003-3311-2220 <https://orcid.org/0000-0003-3311-2220>, Gómez, Abel, Zecchini, Lorena del Valle ORCID: https://orcid.org/0000-0002-2284-3266 <https://orcid.org/0000-0002-2284-3266>, Lapunzina, Pablo ORCID: https://orcid.org/0000-0002-6324-4825 <https://orcid.org/0000-0002-6324-4825>, Aza Carmona, Miriam ORCID: https://orcid.org/0000-0003-4448-9541 <https://orcid.org/0000-0003-4448-9541>, Heath, Karen E. ORCID: https://orcid.org/0000-0002-5816-7044 <https://orcid.org/0000-0002-5816-7044> and Asteggiano, Carla Gabriela ORCID: https://orcid.org/0000-0003-4713-2775 <https://orcid.org/0000-0003-4713-2775> (2022) Clinical and Genetic Analysis of Multiple Osteochondromas in a Cohort of Argentine Patients. Genes (13).
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reponame_str Producción Académica (UCC)
collection Producción Académica (UCC)
instname_str Universidad Católica de Córdoba
repository.name.fl_str_mv Producción Académica (UCC) - Universidad Católica de Córdoba
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