ArticleBlood2020
Enhancer-gene rewiring in the pathogenesis of Quebec platelet disorder.
Article in Blood, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
13 citing papers in PubMed, 25 citations in OpenAlex.
- Investigator-Led Research to Improve the Diagnostic Assessment of Platelet Function Disorders: Reflections on the Challenges and Rewards.International journal of laboratory hematology · 2026Review
- Molecular Pathogenesis of Inherited Platelet Dysfunction.Biomolecules · 2025Review
- Cerebral sinus venous thrombosis in a child with Québec platelet disorder with high-resolution intracellular localization of urokinase in platelets.Research and practice in thrombosis and haemostasis · 2025Article
- The Role of Platelet Dysfunctions in the Pathogenesis of the Hemostatic-Coagulant System Imbalances.International journal of molecular sciences · 2025Review
- Molecular characterization of positively selected genes contributing aquatic adaptation in marine mammals.Genes & genomics · 2024Article
- Three-dimensional genome structure and function.MedComm · 2023Review
- Whole genome sequencing identifies structural variants contributing to hematologic traits in the NHLBI TOPMed program.Nature communications · 2022Article
- Non-coding genetic variation in regulatory elements determines thrombosis and hemostasis phenotypes.Journal of thrombosis and haemostasis : JTH · 2022Review
- Duplications disrupt chromatin architecture and rewire GPR101-enhancer communication in X-linked acrogigantism.American journal of human genetics · 2022Article
- Transcriptomic analysis reveals myometrial topologically associated domains linked to the onset of human term labour.Molecular human reproduction · 2022Article
- A tandem duplication in Drosophila melanogaster shows enhanced expression beyond the gene copy number.Genetics · 2022Article
- Inherited Platelet Disorders: An Updated Overview.International journal of molecular sciences · 2021Review
- Heart Enhancers: Development and Disease Control at a Distance.Frontiers in genetics · 2021Review
Corrections and comments
- Commented on by
Authors and funding
15 authors at 4 institutions in 1 country.
Funding
Abstract
Quebec platelet disorder (QPD) is an autosomal dominant bleeding disorder with a unique, platelet-dependent, gain-of-function defect in fibrinolysis, without systemic fibrinolysis. The hallmark feature of QPD is a >100-fold overexpression of PLAU, specifically in megakaryocytes. This overexpression leads to a >100-fold increase in platelet stores of urokinase plasminogen activator (PLAU/uPA); subsequent plasmin-mediated degradation of diverse α-granule proteins; and platelet-dependent, accelerated fibrinolysis. The causative mutation is a 78-kb tandem duplication of PLAU. How this duplication causes megakaryocyte-specific PLAU overexpression is unknown. To investigate the mechanism that causes QPD, we used epigenomic profiling, comparative genomics, and chromatin conformation capture approaches to study PLAU regulation in cultured megakaryocytes from participants with QPD and unaffected controls. QPD duplication led to ectopic interactions between PLAU and a conserved megakaryocyte enhancer found within the same topologically associating domain (TAD). Our results support a unique disease mechanism whereby the reorganization of sub-TAD genome architecture results in a dramatic, cell-type-specific blood disorder phenotype.
Indexed as
Identifiers
What OpenQuestion holds
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.