Genetic analyses of aplastic anemia and idiopathic pulmonary fibrosis patients with short telomeres, possible implication of DNA-repair genes

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 UriaCristina Diaz-Heredia, Claudia Valenzuela, Belén López-Muñiz, Pablo Lapunzina, Julian Sevilla, María Molina-Molina, Rosario Perona, Leandro Sastre

Research output: Contribution to journalArticleResearch

18 Citations (Scopus)


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.
Original languageEnglish
Article number82
Pages (from-to)82
Number of pages12
JournalOrphanet Journal of Rare Diseases
Issue number1
Publication statusPublished - 17 Apr 2019


  • Adolescent
  • Adult
  • Anemia, Aplastic/genetics
  • Aplastic anemia
  • Child
  • Child, Preschool
  • DNA Repair/genetics
  • DNA repair
  • Dyskeratosis Congenita/genetics
  • Dyskeratosis congenita
  • Exons/genetics
  • Female
  • Humans
  • Infant
  • Male
  • Pedigree
  • Pulmonary Fibrosis/genetics
  • Pulmonary fibrosis
  • RNA/genetics
  • Telomerase/genetics
  • Telomere
  • Telomere Shortening/genetics
  • Telomere/genetics
  • Telomeropathies
  • Young Adult


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