ArticleHuman mutation2019
From incomplete penetrance with normal telomere length to severe disease and telomere shortening in a family with monoallelic and biallelic PARN pathogenic variants.
Article in Human mutation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 2 syntheses or guidelines pooled it, 28 citations in OpenAlex.
- Guideline
- Pulmonary fibrosis in dyskeratosis congenita: a case report with a PRISMA-compliant systematic review.BMC pulmonary medicine · 2021Pooled it
- Genetic influences on haematopoiesis.Nature reviews. Genetics · 2026Review
- A Proposed Clinical Diagnostic Framework for Short Telomere Syndrome.Clinical genetics · 2026Review
- Advances in our understanding of distal progenitors in idiopathic pulmonary fibrosis: implications for novel therapeutics.The European respiratory journal · 2026Review
- Clonal Signatures of Telomere Biology Disorders.Current hematologic malignancy reports · 2026Review
- The Impact of Genetics on Pediatric Interstitial Lung Diseases: A Narrative Literature Review and Clinical Implications.Biomedicines · 2026Review
- Germline PARN Variants in Telomere Biology Disorders and Challenges in Variant Curation.Molecular genetics & genomic medicine · 2025Article
- A non-resolving cough in a 41-year-old woman: a case of familial pulmonary fibrosis.Breathe (Sheffield, England) · 2025Article
- Hematological complications in solid organ transplant recipients with telomere biology disorders: a narrative review.Frontiers in immunology · 2025Review
- Genotype and Associated Cancer Risk in Individuals With Telomere Biology Disorders.JAMA network open · 2024Article
- Telomeres: Dysfunction, Maintenance, Aging and Cancer.Aging and disease · 2023Review
- A distal lung organoid model to study interstitial lung disease, viral infection and human lung development.Nature protocols · 2023Review
- Telomere biology disorders.NPJ genomic medicine · 2021Review
- Human mutational constraint as a tool to understand biology of rare and emerging bone marrow failure syndromes.Blood advances · 2020Article
- Telomere biology disorder prevalence and phenotypes in adults with familial hematologic and/or pulmonary presentations.Blood advances · 2020Article
- CD8Journal of clinical laboratory analysis · 2020Article
- Regulation of poly(a)-specific ribonuclease activity by reversible lysine acetylation.The Journal of biological chemistry · 2020Article
- Molecular Interplay of PARN and Telomerase: Tail Modifiers and Disease Implications.Wiley interdisciplinary reviews. RNAReview
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
Abstract
PARN encodes poly(A)-specific ribonuclease. Biallelic and monoallelic PARN variants are associated with Hoyeraal-Hreidarsson syndrome/dyskeratosis congenita and idiopathic pulmonary fibrosis (IPF), respectively. The molecular features associated with incomplete penetrance of PARN-associated IPF have not been described. We report a family with a rare missense, p.Y91C, and a novel insertion, p.(I274*), PARN variant. We found PARN p.Y91C had reduced deadenylase activity and the p.(I274*) transcript was depleted. Detailed analysis of the consequences of these variants revealed that, while PARN protein was lowest in the severely affected biallelic child who had the shortest telomeres, it was also reduced in his mother with the p.(I274*) variant but telomeres at the 50th percentile. Increased adenylation of telomerase RNA, human telomerase RNA, and certain small nucleolar RNAs, and impaired ribosomal RNA maturation were observed in cells derived from the severely affected biallelic carrier, but not in the other, less affected biallelic carrier, who had less severely shortened telomeres, nor in the monoallelic carriers who were unaffected and had telomeres ranging from the 1st to the 50th percentiles. We identified hsa-miR-202-5p as a potential negative regulator of PARN. We propose one or more genetic modifiers influence the impact of PARN variants on its targets and this underlies incomplete penetrance of PARN-associated disease.
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Registered trials
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.