ArticleChest2020
Synonymous Mutation in DKC1 Causes Telomerase RNA Insufficiency Manifesting as Familial Pulmonary Fibrosis.
Article in Chest, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 39 citations in OpenAlex.
- Telomere-associated non-malignant pulmonary diseases: Pathogenic mechanisms and therapeutic strategies.Acta pharmaceutica Sinica. B · 2026Review
- Clonal Signatures of Telomere Biology Disorders.Current hematologic malignancy reports · 2026Review
- Adult male patients withERJ open research · 2026Article
- Whole exome sequencing identified two novel mutations ofFrontiers in cell and developmental biology · 2026Article
- Severe nonketotic hyperglycinaemia due to a synonymous variant.Molecular genetics and metabolism reports · 2025Article
- RNA splicing: Novel star in pulmonary diseases with a treatment perspective.Acta pharmaceutica Sinica. B · 2025Review
- Viewpoint: Pre- and post-lung transplant considerations for patients with ultra-short telomere length.The European respiratory journal · 2025Article
- Telomeropathies in Interstitial Lung Disease and Lung Transplant Recipients.Journal of clinical medicine · 2025Review
- Progressive lung fibrosis: reprogramming a genetically vulnerable bronchoalveolar epithelium.The Journal of clinical investigation · 2025Review
- Hematological complications in solid organ transplant recipients with telomere biology disorders: a narrative review.Frontiers in immunology · 2025Review
- Telomeres: Dysfunction, Maintenance, Aging and Cancer.Aging and disease · 2023Review
- Investigation of Gene Networks in Three Components of Immune System Provides Novel Insights into Immune Response Mechanisms againstAnimals : an open access journal from MDPI · 2023Article
- Article
- T cell immune deficiency rather than chromosome instability predisposes patients with short telomere syndromes to squamous cancers.Cancer cell · 2023Article
- Genomic Fingerprint Associated with Familial Idiopathic Pulmonary Fibrosis: A Review.International journal of medical sciences · 2023Review
- The Genetic and Epigenetic Footprint in Idiopathic Pulmonary Fibrosis and Familial Pulmonary Fibrosis: A State-of-the-Art Review.Diagnostics (Basel, Switzerland) · 2022Review
- Genetics in Idiopathic Pulmonary Fibrosis: A Clinical Perspective.Diagnostics (Basel, Switzerland) · 2022Review
- Telomere-mediated lung disease.Physiological reviews · 2022Review
- The Role of Telomeres in Human Disease.Annual review of genomics and human genetics · 2022Review
- Editing TINF2 as a potential therapeutic approach to restore telomere length in dyskeratosis congenita.Blood · 2022Article
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundIdiopathic pulmonary fibrosis (IPF) is the most common of short telomere phenotypes. Familial clustering of IPF is common, but the genetic basis remains unknown in more than one-half of cases. We identified a 65-year-old man with familial IPF, short telomere length, and low telomerase RNA levels. He was diagnosed with a short telomere syndrome after developing hematologic complications post-lung transplantation, but no mutations were identified in a clinical testing pipeline. RESEARCH QUESTION: What is the molecular basis underlying the familial IPF and low telomerase RNA levels in this patient? STUDY DESIGN AND
methodsWe analyzed whole-genome sequence data and performed functional molecular studies on cells derived from the patient and his family.
resultsWe identified a previously unreported synonymous variant c.942G>A p.K314K in DKC1, the gene encoding the dyskerin ribonucleoprotein, which is required for telomerase RNA biogenesis. The mutation created a competing de novo exonic splicing enhancer, and the misspliced product was degraded by nonsense-mediated decay causing an overall dyskerin deficiency in mutation carriers. In silico tools identified other rare silent DKC1 variants that warrant functional evaluation if found in patients with short telomere-mediated disease.
interpretationOur data point to silent mutation in telomere maintenance genes as a mechanism of familial pulmonary fibrosis. In contrast to DKC1 missense mutations, which primarily manifest in children as dyskeratosis congenita, hypomorphic mutations affecting dyskerin levels likely have a predilection to presenting in adults as pulmonary fibrosis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.