Genetic analyses of aplastic anemia and idiopathic pulmonary fibrosis patients with short telomeres, possible implication of DNA-repair genes
Background: Telomeres are nucleoprotein structures present at the terminal region of the chromosomes. Mutations in genes coding for proteins involved in telomere maintenance are causative of a number of disorders known as telomeropathies. The genetic origin of these diseases is heterogeneous and has...
| Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2019 |
| País: | España |
| Institución: | Universitat Autònoma de Barcelona |
| Repositorio: | Dipòsit Digital de Documents de la UAB |
| Idioma: | inglés |
| OAI Identifier: | oai:ddd.uab.cat:223237 |
| Acceso en línea: | https://ddd.uab.cat/record/223237 https://dx.doi.org/urn:doi:10.1186/s13023-019-1046-0 |
| Access Level: | acceso abierto |
| Palabra clave: | Telomere Dyskeratosis congenita Pulmonary fibrosis Aplastic anemia Telomeropathies DNA repair |
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Genetic analyses of aplastic anemia and idiopathic pulmonary fibrosis patients with short telomeres, possible implication of DNA-repair genesGarcía Arias-Salgado, ElenaGálvez, EvaPlanas-Cerezales, Lurdes|||0000-0001-7636-444XPintado-Berninches, Laura|||0000-0002-3331-7130Vallespín, Elena|||0000-0002-8080-8629Martínez, PilarCarrillo García, Jaime|||0000-0002-2861-3015Iarriccio, LauraRuiz-Llobet, Anna|||0000-0002-0155-7922Català, Albert|||0000-0003-0133-1752Badell Serra, Isabel|||0000-0001-6546-2175Gonzalez-Granado, Luis Ignacio|||0000-0001-6917-8980Martín-Nalda, Andrea|||0000-0002-1715-153XMartínez Gallo, Mónica|||0000-0002-7340-2161Galera, AnaRodríguez-Vigil, CarmenBastos, Mariana|||0000-0002-9431-4646Pérez de Nanclares, Guiomar|||0000-0002-2424-5294Leiro-Fernández, VirginiaUria Oficialdegui, Maria Luz|||0000-0002-1384-999XDíaz de Heredia, Cristina|||0000-0001-8086-296XValenzuela, Claudia|||0000-0002-0856-6290Martín Alegre, Sara|||0000-0002-0619-9255López-Muñiz, BelénLapunzina, Pablo|||0000-0002-6324-4825Sevilla, Julián|||0000-0002-6852-1860Molina Molina, Maria|||0000-0002-1852-1723Perona, Rosario|||0000-0002-2973-5153Sastre, Leandro|||0000-0003-3613-5938TelomereDyskeratosis congenitaPulmonary fibrosisAplastic anemiaTelomeropathiesDNA repairBackground: Telomeres are nucleoprotein structures present at the terminal region of the chromosomes. Mutations in genes coding for proteins involved in telomere maintenance are causative of a number of disorders known as telomeropathies. The genetic origin of these diseases is heterogeneous and has not been determined for a significant proportion of patients. Methods: This article describes the genetic characterization of a cohort of patients. Telomere length was determined by Southern blot and quantitative PCR. Nucleotide variants were analyzed either by high-resolution melting analysis and Sanger sequencing of selected exons or by massive sequencing of a panel of genes. Results: Forty-seven patients with telomere length below the 10% of normal population, affected with three telomeropathies: dyskeratosis congenita (4), aplastic anemia (22) or pulmonary fibrosis (21) were analyzed. Eighteen of these patients presented known pathogenic or novel possibly pathogenic variants in the telomere-related genes TERT, TERC, RTEL1, CTC1 and ACD. In addition, the analyses of a panel of 188 genes related to haematological disorders indicated that a relevant proportion of the patients (up to 35%) presented rare variants in genes related to DNA repair or in genes coding for proteins involved in the resolution of complex DNA structures, that participate in telomere replication. Mutations in some of these genes are causative of several syndromes previously associated to telomere shortening. Conclusion: Novel variants in telomere, DNA repair and replication genes are described that might indicate the contribution of variants in these genes to the development of telomeropathies. Patients carrying variants in telomere-related genes presented worse evolution after diagnosis than the rest of patients analyzed. 22019-01-0120192019-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/223237https://dx.doi.org/urn:doi:10.1186/s13023-019-1046-0reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengInstituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI17-01401Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI14-01495open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2232372026-06-06T12:50:31Z |
| dc.title.none.fl_str_mv |
Genetic analyses of aplastic anemia and idiopathic pulmonary fibrosis patients with short telomeres, possible implication of DNA-repair genes |
| title |
Genetic analyses of aplastic anemia and idiopathic pulmonary fibrosis patients with short telomeres, possible implication of DNA-repair genes |
| spellingShingle |
Genetic analyses of aplastic anemia and idiopathic pulmonary fibrosis patients with short telomeres, possible implication of DNA-repair genes García Arias-Salgado, Elena Telomere Dyskeratosis congenita Pulmonary fibrosis Aplastic anemia Telomeropathies DNA repair |
| title_short |
Genetic analyses of aplastic anemia and idiopathic pulmonary fibrosis patients with short telomeres, possible implication of DNA-repair genes |
| title_full |
Genetic analyses of aplastic anemia and idiopathic pulmonary fibrosis patients with short telomeres, possible implication of DNA-repair genes |
| title_fullStr |
Genetic analyses of aplastic anemia and idiopathic pulmonary fibrosis patients with short telomeres, possible implication of DNA-repair genes |
| title_full_unstemmed |
Genetic analyses of aplastic anemia and idiopathic pulmonary fibrosis patients with short telomeres, possible implication of DNA-repair genes |
| title_sort |
Genetic analyses of aplastic anemia and idiopathic pulmonary fibrosis patients with short telomeres, possible implication of DNA-repair genes |
| dc.creator.none.fl_str_mv |
García Arias-Salgado, Elena Gálvez, Eva Planas-Cerezales, Lurdes|||0000-0001-7636-444X Pintado-Berninches, Laura|||0000-0002-3331-7130 Vallespín, Elena|||0000-0002-8080-8629 Martínez, Pilar Carrillo García, Jaime|||0000-0002-2861-3015 Iarriccio, Laura Ruiz-Llobet, Anna|||0000-0002-0155-7922 Català, Albert|||0000-0003-0133-1752 Badell Serra, Isabel|||0000-0001-6546-2175 Gonzalez-Granado, Luis Ignacio|||0000-0001-6917-8980 Martín-Nalda, Andrea|||0000-0002-1715-153X Martínez Gallo, Mónica|||0000-0002-7340-2161 Galera, Ana Rodríguez-Vigil, Carmen Bastos, Mariana|||0000-0002-9431-4646 Pérez de Nanclares, Guiomar|||0000-0002-2424-5294 Leiro-Fernández, Virginia Uria Oficialdegui, Maria Luz|||0000-0002-1384-999X Díaz de Heredia, Cristina|||0000-0001-8086-296X Valenzuela, Claudia|||0000-0002-0856-6290 Martín Alegre, Sara|||0000-0002-0619-9255 López-Muñiz, Belén Lapunzina, Pablo|||0000-0002-6324-4825 Sevilla, Julián|||0000-0002-6852-1860 Molina Molina, Maria|||0000-0002-1852-1723 Perona, Rosario|||0000-0002-2973-5153 Sastre, Leandro|||0000-0003-3613-5938 |
| author |
García Arias-Salgado, Elena |
| author_facet |
García Arias-Salgado, Elena Gálvez, Eva Planas-Cerezales, Lurdes|||0000-0001-7636-444X Pintado-Berninches, Laura|||0000-0002-3331-7130 Vallespín, Elena|||0000-0002-8080-8629 Martínez, Pilar Carrillo García, Jaime|||0000-0002-2861-3015 Iarriccio, Laura Ruiz-Llobet, Anna|||0000-0002-0155-7922 Català, Albert|||0000-0003-0133-1752 Badell Serra, Isabel|||0000-0001-6546-2175 Gonzalez-Granado, Luis Ignacio|||0000-0001-6917-8980 Martín-Nalda, Andrea|||0000-0002-1715-153X Martínez Gallo, Mónica|||0000-0002-7340-2161 Galera, Ana Rodríguez-Vigil, Carmen Bastos, Mariana|||0000-0002-9431-4646 Pérez de Nanclares, Guiomar|||0000-0002-2424-5294 Leiro-Fernández, Virginia Uria Oficialdegui, Maria Luz|||0000-0002-1384-999X Díaz de Heredia, Cristina|||0000-0001-8086-296X Valenzuela, Claudia|||0000-0002-0856-6290 Martín Alegre, Sara|||0000-0002-0619-9255 López-Muñiz, Belén Lapunzina, Pablo|||0000-0002-6324-4825 Sevilla, Julián|||0000-0002-6852-1860 Molina Molina, Maria|||0000-0002-1852-1723 Perona, Rosario|||0000-0002-2973-5153 Sastre, Leandro|||0000-0003-3613-5938 |
| author_role |
author |
| author2 |
Gálvez, Eva Planas-Cerezales, Lurdes|||0000-0001-7636-444X Pintado-Berninches, Laura|||0000-0002-3331-7130 Vallespín, Elena|||0000-0002-8080-8629 Martínez, Pilar Carrillo García, Jaime|||0000-0002-2861-3015 Iarriccio, Laura Ruiz-Llobet, Anna|||0000-0002-0155-7922 Català, Albert|||0000-0003-0133-1752 Badell Serra, Isabel|||0000-0001-6546-2175 Gonzalez-Granado, Luis Ignacio|||0000-0001-6917-8980 Martín-Nalda, Andrea|||0000-0002-1715-153X Martínez Gallo, Mónica|||0000-0002-7340-2161 Galera, Ana Rodríguez-Vigil, Carmen Bastos, Mariana|||0000-0002-9431-4646 Pérez de Nanclares, Guiomar|||0000-0002-2424-5294 Leiro-Fernández, Virginia Uria Oficialdegui, Maria Luz|||0000-0002-1384-999X Díaz de Heredia, Cristina|||0000-0001-8086-296X Valenzuela, Claudia|||0000-0002-0856-6290 Martín Alegre, Sara|||0000-0002-0619-9255 López-Muñiz, Belén Lapunzina, Pablo|||0000-0002-6324-4825 Sevilla, Julián|||0000-0002-6852-1860 Molina Molina, Maria|||0000-0002-1852-1723 Perona, Rosario|||0000-0002-2973-5153 Sastre, Leandro|||0000-0003-3613-5938 |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
Telomere Dyskeratosis congenita Pulmonary fibrosis Aplastic anemia Telomeropathies DNA repair |
| topic |
Telomere Dyskeratosis congenita Pulmonary fibrosis Aplastic anemia Telomeropathies DNA repair |
| description |
Background: Telomeres are nucleoprotein structures present at the terminal region of the chromosomes. Mutations in genes coding for proteins involved in telomere maintenance are causative of a number of disorders known as telomeropathies. The genetic origin of these diseases is heterogeneous and has not been determined for a significant proportion of patients. Methods: This article describes the genetic characterization of a cohort of patients. Telomere length was determined by Southern blot and quantitative PCR. Nucleotide variants were analyzed either by high-resolution melting analysis and Sanger sequencing of selected exons or by massive sequencing of a panel of genes. Results: Forty-seven patients with telomere length below the 10% of normal population, affected with three telomeropathies: dyskeratosis congenita (4), aplastic anemia (22) or pulmonary fibrosis (21) were analyzed. Eighteen of these patients presented known pathogenic or novel possibly pathogenic variants in the telomere-related genes TERT, TERC, RTEL1, CTC1 and ACD. In addition, the analyses of a panel of 188 genes related to haematological disorders indicated that a relevant proportion of the patients (up to 35%) presented rare variants in genes related to DNA repair or in genes coding for proteins involved in the resolution of complex DNA structures, that participate in telomere replication. Mutations in some of these genes are causative of several syndromes previously associated to telomere shortening. Conclusion: Novel variants in telomere, DNA repair and replication genes are described that might indicate the contribution of variants in these genes to the development of telomeropathies. Patients carrying variants in telomere-related genes presented worse evolution after diagnosis than the rest of patients analyzed. |
| publishDate |
2019 |
| dc.date.none.fl_str_mv |
2 2019-01-01 2019 2019-01-01 |
| dc.type.none.fl_str_mv |
Article http://purl.org/coar/resource_type/c_6501 VoR http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
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article |
| dc.identifier.none.fl_str_mv |
https://ddd.uab.cat/record/223237 https://dx.doi.org/urn:doi:10.1186/s13023-019-1046-0 |
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https://ddd.uab.cat/record/223237 https://dx.doi.org/urn:doi:10.1186/s13023-019-1046-0 |
| dc.language.none.fl_str_mv |
Inglés eng |
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Inglés |
| language |
eng |
| dc.relation.none.fl_str_mv |
Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI17-01401 Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI14-01495 |
| dc.rights.none.fl_str_mv |
open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by/4.0/ |
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info:eu-repo/semantics/openAccess |
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open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by/4.0/ |
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openAccess |
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application/pdf |
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reponame:Dipòsit Digital de Documents de la UAB instname:Universitat Autònoma de Barcelona |
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