Genetic analyses of aplastic anemia and idiopathic pulmonary fibrosis patients with short telomeres, possible implication of DNA-repair genes
García Arias-Salgado, Elena (Advanced Medical Projects)
Gálvez, Eva (Hospital Infantil Universitario Niño Jesús (Madrid))
Planas-Cerezales, Lurdes (Institut d'Investigació Biomèdica de Bellvitge)
Pintado-Berninches, Laura (Advanced Medical Projects)
Vallespín, Elena (Hospital Universitario La Paz (Madrid))
Martínez, Pilar (Hospital Universitario La Paz (Madrid))
Carrillo García, Jaime (Instituto de Investigaciones Biomédicas "Alberto Sols")
Iarriccio, Laura (Advanced Medical Projects)
Ruiz-Llobet, Anna (Institut de Recerca Sant Joan de Déu)
Català, Albert (Institut de Recerca Sant Joan de Déu)
Badell Serra, Isabel (Universitat Autònoma de Barcelona. Departament de Pediatria, Obstetrícia i Ginecologia i Medicina Preventiva i Salut Pública)
Gonzalez-Granado, Luis Ignacio (Hospital Universitario 12 de Octubre (Madrid))
Martín-Nalda, Andrea (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Martínez Gallo, Mónica (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Galera, Ana (Hospital Universitario Virgen de la Arrixaca (Múrcia))
Rodríguez-Vigil, Carmen (Hospital Universitario Miguel Servet (Saragossa))
Bastos, Mariana (Hospital General Universitario Gregorio Marañón. Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM))
Pérez de Nanclares, Guiomar (Instituto de Investigación Sanitaria Bioaraba (Vitoria, País Basc))
Leiro-Fernández, Virginia (Instituto de Investigación Biomédica de Vigo)
Uria Oficialdegui, Maria Luz (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Díaz de Heredia, Cristina (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Valenzuela, Claudia (Hospital Universitario de la Princesa (Madrid))
Martín, Sara (Institut d'Investigació Biomèdica de Bellvitge)
López-Muñiz, Belén (Hospital Universitario Infanta Leonor)
Lapunzina, Pablo (Centro de Investigación Biomédica en Red de Enfermedades Raras)
Sevilla, Julián (Centro de Investigación Biomédica en Red de Enfermedades Raras)
Molina Molina, Maria (Centro de Investigación Biomédica en Red de Enfermedades Respiratorias)
Perona, Rosario (Centro de Investigación Biomédica en Red de Enfermedades Raras)
Sastre, Leandro (Centro de Investigación Biomédica en Red de Enfermedades Raras)

Data:	2019
Resum:	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.
Ajuts:	Instituto de Salud Carlos III PI17-01401 Instituto de Salud Carlos III PI14-01495
Nota:	Altres ajuts: Funded by one ACCI project from CIBERER and one grant to the FPI cohort from CIBERES.
Drets:	Aquest 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.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Telomere ; Dyskeratosis congenita ; Pulmonary fibrosis ; Aplastic anemia ; Telomeropathies ; DNA repair
Publicat a:	Orphanet Journal of Rare Diseases, Vol. 14 Núm. 1 (17 2019) , p. 82, ISSN 1750-1172

DOI: 10.1186/s13023-019-1046-0
PMID: 30995915

12 p, 3.3 MB

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