Trial reportProceedings of the National Academy of Sciences of the United States of America2013
Lymphatic abnormalities are associated with RASA1 gene mutations in mouse and man.
Trial report in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
What it found
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
64 citing papers in PubMed.
- An abnormal lymphatic phenotype is associated with subcutaneous adipose tissue deposits in Dercum's disease.Obesity (Silver Spring, Md.) · 2014Trial
- From Somatic Driver to Molecular Therapy in Retinal, Choroidal and Periocular Vascular Disease: Mosaicism, Targetable Pathways and Ocular Toxicity.International journal of molecular sciences · 2026Review
- Capillary Malformation-Arteriovenous Malformation Syndrome Associated with RASA1 and EPHB4 Mutations: Comparative Case Series and Narrative Review.Life (Basel, Switzerland) · 2026Review
- Mechanisms and treatments of lymphedema.Frontiers in immunology · 2026Review
- EPHB4-RASA1 Inhibition of PIEZO1 Ras Activation Drives Lymphatic Valvulogenesis.Circulation research · 2024Article
- Central conducting lymphatic anomaly: from bench to bedside.The Journal of clinical investigation · 2024Review
- Defining the Functional Influence of Endothelial Cell-Expressed Oncogenic Activating Mutations on Vascular Morphogenesis and Capillary Assembly.The American journal of pathology · 2024Article
- The Role of Inflammation in Lymphedema: A Narrative Review of Pathogenesis and Opportunities for Therapeutic Intervention.International journal of molecular sciences · 2024Review
- An EPHB4-RASA1 signaling complex inhibits shear stress-induced Ras-MAPK activation in lymphatic endothelial cells to promote the development of lymphatic vessel valves.bioRxiv : the preprint server for biology · 2023Article
- Genome-Wide Association Studies for Body Conformation Traits in Korean Holstein Population.Animals : an open access journal from MDPI · 2023Article
- Temporospatial inhibition of Erk signaling is required for lymphatic valve formation.Signal transduction and targeted therapy · 2023Article
- Pathophysiology of Slow-Flow Vascular Malformations: Current Understanding and Unanswered Questions.Journal of vascular anomalies · 2023Review
- Investigation into the genetics of fetal congenital lymphatic anomalies.Prenatal diagnosis · 2023Article
- EPHB4-RASA1-Mediated Negative Regulation of Ras-MAPK Signaling in the Vasculature: Implications for the Treatment of EPHB4- and RASA1-Related Vascular Anomalies in Humans.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Lymphatic contractile dysfunction in mouse models of Cantú Syndrome with KFunction (Oxford, England) · 2023Article
- Imaging peripheral lymphatic dysfunction in chronic conditions.Frontiers in physiology · 2023Review
- Lymphatic Vascular Permeability.Cold Spring Harbor perspectives in medicine · 2022Review
- Molecular Mechanisms Driving Lymphedema and Other Lymphatic Anomalies.Cold Spring Harbor perspectives in medicine · 2022Article
- Lymphatic function and anatomy in early stages of lipedema.Obesity (Silver Spring, Md.) · 2022Article
- Angiogenesis depends upon EPHB4-mediated export of collagen IV from vascular endothelial cells.JCI insight · 2022Article
4 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
Mutations in gene RASA1 have been historically associated with capillary malformation-arteriovenous malformation, but sporadic reports of lymphatic involvement have yet to be investigated in detail. To investigate the impact of RASA1 mutations in the lymphatic system, we performed investigational near-infrared fluorescence lymphatic imaging and confirmatory radiographic lymphangiography in a Parkes-Weber syndrome (PKWS) patient with suspected RASA1 mutations and correlated the lymphatic abnormalities against that imaged in an inducible Rasa1 knockout mouse. Whole-exome sequencing (WES) analysis and validation by Sanger sequencing of DNA from the patient and unaffected biological parents enabled us to identify an early-frameshift deletion in RASA1 that was shared with the father, who possessed a capillary stain but otherwise no overt disease phenotype. Abnormal lymphatic vasculature was imaged in both affected and unaffected legs of the PKWS subject that transported injected indocyanine green dye to the inguinal lymph node and drained atypically into the abdomen and into dermal lymphocele-like vesicles on the groin. Dermal lymphatic hyperplasia and dilated vessels were observed in Rasa1-deficient mice, with subsequent development of chylous ascites. WES analyses did not identify potential gene modifiers that could explain the variability of penetrance between father and son. Nonetheless, we conclude that the RASA1 mutation is responsible for the aberrant lymphatic architecture and functional abnormalities, as visualized in the PKWS subject and in the animal model. Our unique method to combine investigatory near-infrared fluorescence lymphatic imaging and WES for accurate phenoptyping and unbiased genotyping allows the study of molecular mechanisms of lymphatic involvement of hemovascular disorders.
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