Synapse
⌘+K
Synapse
PulseExploreClubsResearchersJournals
Instagram
HomeClubsExplore
December 8, 2025BloodOpen Access

A continuum of inherited telomere dysfunction links TERT rare variants to age-related diseases

View Full Paper
Ask AI
Bookmark
Share

Authors

SWSean WenAstraZeneca (United Kingdom)DGDimitris GazgalisHarvard UniversityFTFrederick D. TsaiBoston Medical Center

Discussion

Loading...

Member takes

Implication

Research demonstrates telomere dysfunction impacts bone marrow failure and clinical phenotypes, suggesting a continuum of TERT variant impairment.

Key Points

  • This research aims to explore the connection between TERT rare variants and their impact on telomere dysfunction and related age-associated diseases.
  • Generated a functional atlas of TERT variants using UK Biobank data.
  • Identified rare TERT variants and quantified their impact on telomere length and cellular assays.
  • Performed molecular simulations to understand functional impairment of TERT variants.
  • 69% of TERT rare variants showed functional impairment with severe and intermediate effects on telomere length.
  • Impairment correlates with clinical phenotypes including bone marrow dysfunction and osteoporosis.
  • Telomere length impacts were more pronounced in severe variants, indicating direct associations with age-related diseases.

Cite This Study

Wen et al. (2025) studied this question.

synapsesocial.com/papers/69362f364fa91c937236d33ehttps://doi.org/10.1182/blood-2025-749
View Full Paper
Ask AI
Bookmark
Share

Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Telomerase activity in T-cells as a functional test for pathogenicity assessment of novel genetic variants in telomere biology disorders2025 · 2 citations
  2. 2Germline RTEL1 Variants in Telomere Biology Disorders2024 · 8 citations
  3. 3Case Series: Clinical Significance of Heterozygous Pathogenic RTEL1 Variants Identified via Routine Clinical Genetic Diagnostics2025
  4. 4Abstract 6144: A polymorphic TERT tandem repeat creating an expandable intronic G4 quadruplex is associated with TERT expression, relative leukocyte telomere length and cancer risk2024
  5. 5Association and causal impact of TERT genetic variants on peripheral blood leukocyte telomere length and cerebral small vessel disease risk in a Chinese Han population: a mendelian randomization analysis2024 · 1 citations