Genetic analyses of aplastic anemia and idiopathic pulmonary fibrosis patients with short telomeres, possible implication of DNA-repair genes
Abstract 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...
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BMC
2019-04-01
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Series: | Orphanet Journal of Rare Diseases |
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Online Access: | http://link.springer.com/article/10.1186/s13023-019-1046-0 |
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Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Elena G. Arias-Salgado Eva Galvez Lurdes Planas-Cerezales Laura Pintado-Berninches Elena Vallespin Pilar Martinez Jaime Carrillo Laura Iarriccio Anna Ruiz-Llobet Albert Catalá Isabel Badell-Serra Luis I. Gonzalez-Granado Andrea Martín-Nalda Mónica Martínez-Gallo Ana Galera-Miñarro Carmen Rodríguez-Vigil Mariana Bastos-Oreiro Guiomar Perez de Nanclares Virginia Leiro-Fernández Maria-Luz Uria Cristina Diaz-Heredia Claudia Valenzuela Sara Martín Belén López-Muñiz Pablo Lapunzina Julian Sevilla María Molina-Molina Rosario Perona Leandro Sastre |
spellingShingle |
Elena G. Arias-Salgado Eva Galvez Lurdes Planas-Cerezales Laura Pintado-Berninches Elena Vallespin Pilar Martinez Jaime Carrillo Laura Iarriccio Anna Ruiz-Llobet Albert Catalá Isabel Badell-Serra Luis I. Gonzalez-Granado Andrea Martín-Nalda Mónica Martínez-Gallo Ana Galera-Miñarro Carmen Rodríguez-Vigil Mariana Bastos-Oreiro Guiomar Perez de Nanclares Virginia Leiro-Fernández Maria-Luz Uria Cristina Diaz-Heredia Claudia Valenzuela Sara Martín Belén López-Muñiz Pablo Lapunzina Julian Sevilla María Molina-Molina Rosario Perona Leandro Sastre Genetic analyses of aplastic anemia and idiopathic pulmonary fibrosis patients with short telomeres, possible implication of DNA-repair genes Orphanet Journal of Rare Diseases Telomere Dyskeratosis congenita Pulmonary fibrosis Aplastic anemia DNA repair Telomeropathies |
author_facet |
Elena G. Arias-Salgado Eva Galvez Lurdes Planas-Cerezales Laura Pintado-Berninches Elena Vallespin Pilar Martinez Jaime Carrillo Laura Iarriccio Anna Ruiz-Llobet Albert Catalá Isabel Badell-Serra Luis I. Gonzalez-Granado Andrea Martín-Nalda Mónica Martínez-Gallo Ana Galera-Miñarro Carmen Rodríguez-Vigil Mariana Bastos-Oreiro Guiomar Perez de Nanclares Virginia Leiro-Fernández Maria-Luz Uria Cristina Diaz-Heredia Claudia Valenzuela Sara Martín Belén López-Muñiz Pablo Lapunzina Julian Sevilla María Molina-Molina Rosario Perona Leandro Sastre |
author_sort |
Elena G. Arias-Salgado |
title |
Genetic analyses of aplastic anemia and idiopathic pulmonary fibrosis patients with short telomeres, possible implication of DNA-repair genes |
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 |
publisher |
BMC |
series |
Orphanet Journal of Rare Diseases |
issn |
1750-1172 |
publishDate |
2019-04-01 |
description |
Abstract 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. |
topic |
Telomere Dyskeratosis congenita Pulmonary fibrosis Aplastic anemia DNA repair Telomeropathies |
url |
http://link.springer.com/article/10.1186/s13023-019-1046-0 |
work_keys_str_mv |
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doaj-2395ce84c653431ab41d130f9737dfc82020-11-25T02:22:45ZengBMCOrphanet Journal of Rare Diseases1750-11722019-04-0114111210.1186/s13023-019-1046-0Genetic analyses of aplastic anemia and idiopathic pulmonary fibrosis patients with short telomeres, possible implication of DNA-repair genesElena G. Arias-Salgado0Eva Galvez1Lurdes Planas-Cerezales2Laura Pintado-Berninches3Elena Vallespin4Pilar Martinez5Jaime Carrillo6Laura Iarriccio7Anna Ruiz-Llobet8Albert Catalá9Isabel Badell-Serra10Luis I. Gonzalez-Granado11Andrea Martín-Nalda12Mónica Martínez-Gallo13Ana Galera-Miñarro14Carmen Rodríguez-Vigil15Mariana Bastos-Oreiro16Guiomar Perez de Nanclares17Virginia Leiro-Fernández18Maria-Luz Uria19Cristina Diaz-Heredia20Claudia Valenzuela21Sara Martín22Belén López-Muñiz23Pablo Lapunzina24Julian Sevilla25María Molina-Molina26Rosario Perona27Leandro Sastre28Instituto de Investigaciones Biomedicas CSIC/UAM, IDIPazHospital Niño Jesús, Hematología y HemoterapiaILD Unit Pneumology Department, University Hospital of Bellvitge, IDIBELL, University of BarcelonaInstituto de Investigaciones Biomedicas CSIC/UAM, IDIPazInstitute of Medical and Molecular Genetics (INGEMM), Hospital Universitario La PazInstitute of Medical and Molecular Genetics (INGEMM), Hospital Universitario La PazInstituto de Investigaciones Biomedicas CSIC/UAM, IDIPazInstituto de Investigaciones Biomedicas CSIC/UAM, IDIPazPediatric Hematology and Oncology Department, Hospital Sant Joan de Déu, University of BarcelonaPediatric Hematology and Oncology Department, Hospital Sant Joan de Déu, University of BarcelonaHospital de la Santa Creu i Sant PauHospital 12 de OctubreImmunology Division, Pediatric Infectious Diseases and Immunodeficiencies Unit, Hospital Universitari Vall d’Hebron (HUVH), Vall d’Hebron Research Institute (VHIR), Department of Cell Biology, Physiology and Immunology, Autonomous University of Barcelona (UAB)Immunology Division, Pediatric Infectious Diseases and Immunodeficiencies Unit, Hospital Universitari Vall d’Hebron (HUVH), Vall d’Hebron Research Institute (VHIR), Department of Cell Biology, Physiology and Immunology, Autonomous University of Barcelona (UAB)Hospital Universitario Virgen de la ArrixacaHospital Miguel ServetHospital Universitario Gregorio Marañon, IiSGMMolecular (Epi)Genetics Laboratory, BioAraba National Health Institute, OSI Araba University HospitalPneumology Department, Hospital Álvaro Cunqueiro, Complexo Hospitalario Universitario de Vigo, NeumoVigoI+i Research Group, Vigo Biomedical Research Institute (IBIV)Immunology Division, Pediatric Infectious Diseases and Immunodeficiencies Unit, Hospital Universitari Vall d’Hebron (HUVH), Vall d’Hebron Research Institute (VHIR), Department of Cell Biology, Physiology and Immunology, Autonomous University of Barcelona (UAB)Immunology Division, Pediatric Infectious Diseases and Immunodeficiencies Unit, Hospital Universitari Vall d’Hebron (HUVH), Vall d’Hebron Research Institute (VHIR), Department of Cell Biology, Physiology and Immunology, Autonomous University of Barcelona (UAB)Hospital de La PrincesaILD Unit Pneumology Department, University Hospital of Bellvitge, IDIBELL, University of BarcelonaHospital Infanta LeonorInstitute of Medical and Molecular Genetics (INGEMM), Hospital Universitario La PazHospital Niño Jesús, Hematología y HemoterapiaILD Unit Pneumology Department, University Hospital of Bellvitge, IDIBELL, University of BarcelonaInstituto de Investigaciones Biomedicas CSIC/UAM, IDIPazInstituto de Investigaciones Biomedicas CSIC/UAM, IDIPazAbstract 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.http://link.springer.com/article/10.1186/s13023-019-1046-0TelomereDyskeratosis congenitaPulmonary fibrosisAplastic anemiaDNA repairTelomeropathies |