| Topic area | Citation (first author year) | Publication date (month/year) | Journal or source | URL/DOI | PMID | Key evidence points (1-2) |
|---|---|---|---|---|---|---|
| Authoritative clinical definition / management overview | Byers 2025 | Feb 2025 | GeneReviews / Definitions | https://doi.org/10.32388/y374vq | 20301667 | Defines vEDS/EDS type IV by arterial, intestinal, and uterine fragility with thin translucent skin and easy bruising; diagnosis is established by a heterozygous pathogenic COL3A1 variant. Recommends multidisciplinary care, periodic arterial screening, BP monitoring, and avoidance of high-risk invasive procedures; pregnancy carries substantial maternal risk. (pqac-00000006, pqac-00000009) |
| National service cohort / surveillance and medication practice | Bowen 2023 | Mar 2023 | European Journal of Human Genetics | https://doi.org/10.1038/s41431-023-01343-7 | not in retrieved text | UK molecularly confirmed cohort: 180 total patients, 126 in statistical analysis. Retrospective data suggested fewer vascular events in patients on long-term ARB and/or beta-blocker therapy; annual MRA-based surveillance and emergency information systems were emphasized. (pqac-00000014, pqac-00000011, pqac-00000017) |
| Arterial lesion distribution / genotype-phenotype | Adham 2022 | Oct 2022 | Frontiers in Cardiovascular Medicine | https://doi.org/10.3389/fcvm.2022.953894 | not in retrieved text | In 330 adults, 82.4% had arterial lesions; 80.6% carried dominant-negative and 19.4% haploinsufficient variants. Dominant-negative variants were associated with more medium-sized artery lesions and lower carotid stiffness; imaging was systematically performed at initial workup. (pqac-00000001, pqac-00000018) |
| Natural history / survival by mutation class | Pepin 2014 | Dec 2014 | Genetics in Medicine | https://doi.org/10.1038/gim.2014.72 | not in retrieved text | Reviewed 1,231 affected individuals; missense and splice-site variants accounted for >90% of 572 COL3A1 alterations. Median survival was 51 years and varied by sex and mutation type, supporting genotype-informed counseling and trial design. (pqac-00000020) |
| Haploinsufficiency mechanism | Schwarze 2001 | Nov 2001 | American Journal of Human Genetics | https://doi.org/10.1086/324123 | not in retrieved text | Identified frameshift/nonsense variants causing COL3A1 haploinsufficiency via nonsense-mediated decay or unstable truncated protein. Presenting features were vascular aneurysm or rupture, showing that reduced type III procollagen alone can produce a vEDS-overlapping phenotype. (pqac-00000019) |
| Fibroblast transcriptomics / ECM disarray | Chiarelli 2018 | Jan 2018 | PLOS ONE | https://doi.org/10.1371/journal.pone.0191220 | not in retrieved text | Dermal fibroblasts with dominant-negative COL3A1 mutations showed altered ER/redox homeostasis and disrupted ECM organization, with reduced fibrillins, EMILINs, elastin, perlecan, decorin, and versican. Supports a mechanism beyond simple collagen deficiency, involving intracellular stress and defective matrix assembly. (pqac-00000016) |
| Collagen fibril ultrastructure / phenotype variability | Ishikawa 2023 | Aug 2023 | Frontiers in Genetics | https://doi.org/10.3389/fgene.2023.1238209 | not in retrieved text | Electron microscopy study of 30 vEDS skin samples found significantly increased irregularity of collagen fibril size versus controls. Some patients had lower fibril irregularity and fewer severe complications, suggesting ER stress and fibrillogenesis modifiers may contribute to phenotypic variability. (pqac-00000000) |
| Medical prevention review / celiprolol evidence | Buso 2024 | Jul 2024 | Journal of Clinical Medicine | https://doi.org/10.3390/jcm13144255 | not in retrieved text | Narrative review summarizes that celiprolol showed a 64% reduction in arterial rupture/dissection risk in BBEST, but overall drug evidence remains limited. Reviews possible celiprolol mechanisms and notes no other medication has clear clinical proof, while ARBs showed benefit in mouse models. (pqac-00000002, pqac-00000015) |
| Real-world celiprolol outcomes | Buso 2024 | Dec 2024 | Vascular Medicine | https://doi.org/10.1177/1358863x231215330 | not in retrieved text | Italian referral-center cohort of 26 genetically confirmed patients: all were on celiprolol at last follow-up and 80% reached 400 mg/day, yet yearly symptomatic vascular event risk remained 8.8%. Confirms tolerability but also persistent residual risk despite therapy. (pqac-00000008) |
| Mechanistic review / collagen III biology | Omar 2021 | Dec 2021 | Matrix Biology Plus | https://doi.org/10.1016/j.mbplus.2021.100090 | not in retrieved text | Reviews collagen III structure-function and explains why COL3A1 defects particularly affect vasculature and hollow organs; emphasizes Gly-X-Y repeat biology and mechanistic heterogeneity. Summarizes core phenotypes including arterial, gastrointestinal, uterine, skin, bruising, and pneumothorax manifestations. (pqac-00000007) |


*Table: This table summarizes the main vascular Ehlers-Danlos syndrome references retrieved in the session, organized by topic and annotated with the most relevant evidence points. It is useful as a compact citation map for drafting a disease entry or dismech YAML evidence section.*